The Role of Leukemia Inhibitory Factor in Cancer and Cancer Metastasis

  • Farhad Ravandi
  • Zeev Estrov
Part of the Cancer Metastasis - Biology and Treatment book series (CMBT, volume 2)


Leukemia inhibitory factor (LIF) is a cytokine that exerts pleiotropic activities. LIF is a member of the interleukin-6 family of cytokines which share a similar receptor complex and signal through the gp 130 receptor subunit. Several neoplastic cells originating from various tissues express either LIF, its receptor, or both and respond to this cytokine. Data accumulated thus far provide a complex picture of LIF activities with LIF being stimulatory, inhibitory or having no effect, depending on the system in which it is studied. LIF appears to play an important role in stimulating the growth of certain tumours, and in affecting the surrounding tissue and the target organ of tumour metastases, particularly bone and skeletal tissue. Overproduction of LIF is likely to have significant constitutional effects. Studies using animal models have shown that LIF induces cachexia, metastatic-type bone calcifications, thrombocytosis, and an abnormal immune response. It is therefore possible that suppression of LIF activity might have a beneficial effect in some cancer patients.

Key words

Leukemia inhibitory factor (LIF) Cancer Metastasis 


  1. 1.
    Kurzrock R, Estrov Z, Wetzler M, Gutterman JU, Talpaz M. LIF: not just a leukemia inhibitory factor. Endocr Rev 1991;12(3):208–17PubMedGoogle Scholar
  2. 2.
    Taupin JL, Pitard V, Dechanet J, Miossec V, Gualde N, Moreau JF. Leukemia inhibitory factor: part of a large ingathering family. Int Rev Immunol 1998;16(3–4):397–26PubMedGoogle Scholar
  3. 3.
    Robinson RC, Grey LM, Staunton D. The crystal structure and biological function of leukemia inhibitory factor: implications for receptor binding. Cell 1994;77:1101–16CrossRefPubMedGoogle Scholar
  4. 4.
    McDonald NQ, Panayotatos N, Hendrickson WA, Crystal structure of dimeric human ciliary neurotrophic factor determined by MAD phasing EMBO J 1995;14:2689–99PubMedGoogle Scholar
  5. 5.
    Somers W, Stahl M, Seehra JS. 1.9 A crystal structure of interleukin 6: implications for a novel mode of receptor dimerization and signaling. EMBO J 1997;16:989–97CrossRefPubMedGoogle Scholar
  6. 6.
    Xu GY, Yu HA, Hong J. Solution structure of recombinant human interleukin-6. J Mol Biol 1997;268:468–81PubMedGoogle Scholar
  7. 7.
    Hinds MG, Maurer T, Zhang JG. Solution structure of leukemia inhibitory factor. J Biol Chem 1998;273:13738–45CrossRefPubMedGoogle Scholar
  8. 8.
    Taga T. Gp130, a shared signal transducing receptor component for menatopoietic and neuropoietic cytokines. J. Neurochem 1996;67:1–10PubMedGoogle Scholar
  9. 9.
    Nakashima K, Taga T. gp130 and the IL-6 family of cytokines: signaling mechanisms and thrombopoirtic activities. Semin Hematol 1998;35:210–21PubMedGoogle Scholar
  10. 10.
    Ishikawa Y. Differentiation of a cell line of myeloid leukemia. J Cell Physiol 1969;74:223–34Google Scholar
  11. 11.
    Tomida M, Yamamoto-Yamaguchi Y, Hozumi M. Purification of a factor inducing differentiation of mouse myeloid leukemic M1 cells from condititioned medium of mouse fibroblast L929 cells. J Biol Chem 1984;259:10978–82PubMedGoogle Scholar
  12. 12.
    Gearing DP, Gough NM, King JA, Hilton DJ, Nicola NA, Simpson RJ, Nice EC, Kelso A, Metcalf D. Molecular cloning and expression of a cDNA encoding a murine myeloid Leukemia Inhibitory Factor. EMBO J 1987;6:3995–02PubMedGoogle Scholar
  13. 13.
    Hilton DJ, Nicola NA, Metcalf D. Purification of a murine leukemia inhibitory factor from Krebs ascitescells. Anal Biochem 1988;173(2):359–67CrossRefPubMedGoogle Scholar
  14. 14.
    Gough NM, Gearing DP, King JA, Willson TA, Hilton DJ, Nicola NA, et al. Molecular cloning and expression of the human homologue of the murine gene encoding myeloid leukemia-inhibitory factor. Proc Natl Acad Sci U S A 1988;85(8):2623–27PubMedGoogle Scholar
  15. 15.
    Hilton DJ, Nicola NA, Gough NM, Metcalf D. Resolution and purification of three distinct factors produced by Krebs ascites cells which have differentiation-inducing activity on murine myeloid leukemic cell lines. J Biol Chem 1988;263(19):9238–43PubMedGoogle Scholar
  16. 16.
    Gearing DP, King JA, Gough NM. Complete sequence of murine leukemia inhibitory factor. Nuleic Acid Res 1988;16:9857Google Scholar
  17. 17.
    Ythier A, Abbud-Filho M, Williams JM, Loertscher R, Schuster MW, Nowill A, Hansen JA, Maltezos D, Strom T. Interleukin 2 dependent release of IL3 activity by T4+ human T-cell clones. Proc Natl Acad Sci USA 1985;82:7020–24PubMedGoogle Scholar
  18. 18.
    Moreau JF, Bonneville M, Peyrat MA, Jacques Y, Soulillou JP. Capacity of alloreactive human T cell clones to produce factor(s) inducing proliferation of the IL3-dependent DA-1 murine cell line. Ann Inst Pasteur Immunol 1986;137C:25–37PubMedGoogle Scholar
  19. 19.
    Moreau JF, Bonneville M, Godard A, Gascan H, Gruart V, Moore MA, et al. Characterization of a factor produced by human T cell clones exhibiting eosinophil-activating and burstpromoting activities. J Immunol 1987;138(11):3844–49PubMedGoogle Scholar
  20. 20.
    Godard A, Gascan H, Naulet J, Peyrat MA, Jacques Y, Soulillou JP, et al. Biochemical characterization and purification of HILDA, a human lymphokine active on eosinophils and bone marrow cells. Blood 1988;71(6):1618–23PubMedGoogle Scholar
  21. 21.
    Moreau JF, Donaldson DD, Bennett F, Witek-Giannotti J, Clark SC, Wong GG. Leukaemia inhibitory factor is identical to the myeloid growth factor human interleukin for DA cells. Nature 1988;336(6200):690–92CrossRefPubMedGoogle Scholar
  22. 22.
    Smith AG, Heath JK, Donaldson DD, Wong GG, Moreau JF, Stahl M, Rogers D. Inhibition of pluripotential embryonic stem cells differentiation by purified polypeptides. Nature 1988;336:688–90PubMedGoogle Scholar
  23. 23.
    Gough NM, Gearing DP, King JA, Wilson TA, Hilton DJ, Nicola NA, Metcalf D. Molecular cloning and expression of the human homologue of the murine gene encoding myeloid Leukemia Inhibitory Factor. Proc Natl Acad Sci USA 1988;88:2623–27Google Scholar
  24. 24.
    Yamamoto-Yamaguchi Y, Tomida M, Hozumi M. Specific binding of a factor inducing differentiation to mouse myeloid leukemic M1 cells. Exp Cell Res 1986;164(1):97–02PubMedGoogle Scholar
  25. 25.
    Lowe DG, Nunes W, Bombara M, McCabe S, Ranges GE, Henzel W, et al. Genomic cloning and heterologous expression of human differentiation-stimulating factor. DNA 1989;8(5):351–59PubMedGoogle Scholar
  26. 26.
    Abe E, Tanaka H, Ishimi Y, Miyaura C, Hayashi T, Nagasawa H, et al. Differentiation-inducing factor purified from conditioned medium of mitogen-treated spleen cell cultures stimulates bone resorption. Proc Natl Acad Sci U S A 1986;83(16):5958–62PubMedGoogle Scholar
  27. 27.
    Smith AG, Hooper ML. Buffalo rat liver cells produce a diffusible activity which inhibits the differentiation of murine embryonal carcinoma and embryonic stem cells. Dev Biol 1987;121(1):1–9CrossRefPubMedGoogle Scholar
  28. 28.
    Koopman P, Cotton RG. A factor produced by feeder cells which inhibits embryonal carcinoma cell differentiation. Characterization and partial purification. Exp Cell Res 1984;154(1):233–42CrossRefPubMedGoogle Scholar
  29. 29.
    Baumann H, Wong GG. Hepatocyte-stimulating factor III shares structural and functional identity with leukemia-inhibitory factor. J Immunol 1989;143(4):1163–67PubMedGoogle Scholar
  30. 30.
    Mori M, Yamaguchi K, Abe K. Purification of a lipoprotein lipase-inhibitory protein produced by a melanoma cell line associated with cancer cachexia. Biochem Biophys Res Commun 1989;160:1085–92CrossRefPubMedGoogle Scholar
  31. 31.
    Cornish J, Gallon K, King A, Edgar S, Reid IR. The effect of leukemia inhibitory factor on bone in vivo. Endocrinology 1993;132;1359–66CrossRefPubMedGoogle Scholar
  32. 32.
    Yamamori T, Fukada K, Aebersold R, Korsching S, Fann MJ, Patterson PH. The cholinergic neuronal differentiation factor from heart cells is identical to leukemia inhibitory factor (published erratum appears in Science 1990 Jan 19:247(4940):271). Science 1989;246(4936):1412–16PubMedGoogle Scholar
  33. 33.
    Williams RL, Hilton DJ, Pease S, Willson TA, Stewart CL, Gearing DP, et al. Myeloid leukaemia inhibitory factor maintains the developmental potential of embryonic stem cells. Nature 1988;336(6200):684–87CrossRefPubMedGoogle Scholar
  34. 34.
    Mori M, Yamaguchi K, Abe K. Purification of a lipoprotein lipase-inhibitory protein produced by a melanoma cell line associated with cancer cachexia. Biochem Biophys Res Commun 1989;160:1085–92CrossRefPubMedGoogle Scholar
  35. 35.
    Gough NM, Williams RL. The pleiotropic actions of leukemia inhibitory factor. Cancer Cells 1989;1(3):77–80PubMedGoogle Scholar
  36. 36.
    Conquet F, Brulet P. Developmental expression of myeloid leukemia inhibitory factor gene in preimplantation blastocysts and in extraembryonic tissue of mouse embryos. Mol Cell Biol 1990;10(7):3801–05PubMedGoogle Scholar
  37. 37.
    Rathjen PD, Nichols J, Tom S, Edwards DR, Heath JK, Smith AG. Developmentally programmed induction of differentiation inhibiting activity and the control of stem cell populations. Genes Dev 1990;4(12B):2308–18PubMedGoogle Scholar
  38. 38.
    Evans MJ, Kaufman MH. Establishment in culture of pluripotential cells from mouse embryos. Nature 1981;292(5819): 154–56CrossRefPubMedGoogle Scholar
  39. 39.
    Pease S, Williams RL. Formation of germ-line chimeras from embryonic stem cells maintained with recombinant leukemia inhibitory factor. Exp Cell Res 1990;190(2):209–11CrossRefPubMedGoogle Scholar
  40. 40.
    Burgess AW. Life after LIF? Bioessays 1989;10(5):166–69CrossRefPubMedGoogle Scholar
  41. 41.
    Shellard J, Perreau J, Brulet P. Role of leukemia inhibitory factor during mammalian development. Eur Cytokine Netw 1996;7(4): 699–12PubMedGoogle Scholar
  42. 42.
    Murphy M, Reid K, Hilton DJ, Bartlett PF. Generation of sensory neurons is stimulated by leukemia inhibitory factor. Proc Natl Acad Sci U S A 1991;88(8):3498–01PubMedGoogle Scholar
  43. 43.
    Billingsley KG, Fraker DL, Strassmann G, Loeser C, Filot HM, Alexander HR. Macrophage-derived tumor necrosis factor and tumor-derived of leukemia inhibitory factor and interleukin-6: possible cellular mechanisms of cancer cachexia. Ann Surg Oncol 1996; 3: 29–35PubMedGoogle Scholar
  44. 44.
    Mori M, Yamaguchi K, Honda S, Nagasaki K, Ueda M, Abe O, Abe K. Cancer cachexia syndrome developed in nude mice bearing melanoma cells producing leukemia-inhibitory factor. Cancer Res 1991; 51(24): 6656–59PubMedGoogle Scholar
  45. 45.
    Ryffel B. Pathology induced by leukemia inhibitory factor. Int Rev Exp Pathol 1993; 34 PTB:69–72PubMedGoogle Scholar
  46. 46.
    Metcalf D, Nicola NA, Gearing DP. Effects of injected leukemia inhibitory factor on hematopoietic and other tissues in mice. Blood 1990;76(1):50–6PubMedGoogle Scholar
  47. 47.
    Metcalf D, Gearing DP. Fatal syndrome in mice engrafted with cells producing high levels of the leukemia inhibitory factor. Proc Natl Acad Sci U S A 1989;86(15):5948–52PubMedGoogle Scholar
  48. 48.
    Metcalf D, Gearing DP. A myelosclerotic syndrome in mice engrafted with cells producing high levels of leukemia inhibitory factor (LIF). Leukemia 1989;3(12):847–52PubMedGoogle Scholar
  49. 49.
    Allan EH, Hilton DJ, Brown MA, Evely RS, Yumita S, Metcalf D, et al. Osteoblasts display receptors for and responses to leukemia-inhibitory factor. J Cell Physiol 1990;145(1):110–29CrossRefPubMedGoogle Scholar
  50. 50.
    Noda M, Vogel RL, Hasson DM, Rodan GA. Leukemia inhibitory factor suppresses proliferation, alkaline phosphatase activity, and type I collagen messenger ribonucleic acid level and enhances osteopontin mRNA level in murine osteoblast-like (MC3T3E1) cells. Endocrinology 1990;127(1):185–90PubMedGoogle Scholar
  51. 51.
    Rodan SB, Wesolowski G, Hilton DJ, Nicola NA, Rodan GA. Leukemia inhibitory factor binds with high affinity to preosteoblastic RCT-1 cells and potentiates the retinoic acid induction of alkaline phosphatase. Endocrinology 1990;127(4):1602–08PubMedGoogle Scholar
  52. 52.
    Reid LR, Lowe C, Cornish J, Skinner SJ, Hilton DJ, Willson TA, et al. Leukemia inhibitory factor: a novel bone-active cytokine. Endocrinology 1990; 126(3): 1416–20PubMedGoogle Scholar
  53. 53.
    Wetzler M, Talpaz M, Lowe DG, Baiocchi G, Gutterman JU, Kurzrock R. Constitutive expression of leukemia inhibitory factor RNA by human bone marrow stromal cells and modulation by IL-1, TNF-alpha, and TGF-beta. Exp Hematol 1991;19(5):347–51PubMedGoogle Scholar
  54. 54.
    Anegon I, Moreau JF, Godard A, Jacques Y, Peyrat MA, Hallet M, et al. Production of human interleukin for DA cells (HILDA)/leukemia inhibitory factor (LIF) by activated monocytes. Cell Immunol 1990;130(1):50–65CrossRefPubMedGoogle Scholar
  55. 55.
    Le PT, Lazorick S, Whichard LP, Yang YC, Clark SC, Haynes BF, Singer KH. Human thymic epithelial cells produce IL-6, granulocyte-monocyte-CSF, and leukemia inhibitory factor. J Immunol 1990; 145:3310PubMedGoogle Scholar
  56. 56.
    Hilton DJ, Nicola NA, Metcalf D. Specific binding of murine leukemia inhibitory factor to normal and leukemic monocytic cells. Proc Natl Acad Sci USA 1988;85:5971–75PubMedGoogle Scholar
  57. 57.
    Baumann H, Jahreis GP, Saunder DN, Koj A. Human keratinocytes and monocytes release factors which regulate the synthesis of major acute phase plasma proteins in hepatic cells from man, rat, and mouse. J Biol Chem 1984;259:7331PubMedGoogle Scholar
  58. 58.
    Gascan H, Anegon I, Praloran V, Naulet J, Godard A, Soulillou JP, Jacques Y. Constitutive production of human interleukin for DA cells/leukemia inhibitory factor by human tumor cell lines derived from various tissues. J Immunol 1990;144:2592PubMedGoogle Scholar
  59. 59.
    Kola I, Davey A, Gough NM. Localization of the murine leukemia inhibitory factor gene near the centromere on chromosome 11. Growth Factors 1990;2(2–3):235–40PubMedGoogle Scholar
  60. 60.
    Sutherland GR, Baker E, Hyland VJ, Callen DF, Stahl J, Gough NM. The gene for human leukemia inhibitory factor (LIF) maps to 22q12. Leukemia 1989;3(1):9–13PubMedGoogle Scholar
  61. 61.
    Budarf M, Emanuel BS, Mohandas T, Goeddel DV, Lowe DG. Human differentiation-stimulating factor (leukemia inhibitory factor, human interleukin DA) gene maps distal to the Ewing sarcoma breakpoint on 22q. Cytogenet Cell Genet 1989;52(1–2): 19–22PubMedGoogle Scholar
  62. 62.
    Gough NM, Wilson TA, Stahl J, Brown MA. Molecular biology of the leukaemia inhibitory factor gene. Ciba Found Symp 1992;167:24–38PubMedGoogle Scholar
  63. 63.
    Gough NM. Molecular genetics of leukemia inhibitory factor (LIF) and its receptor. Growth Factors 1992;7(3):175–79PubMedGoogle Scholar
  64. 64.
    Tomida M, Yamamoto-Yamaguchi Y, Hozumi M. Purification of a factor inducing differentiation of mouse myeloid leukemic M1 cells from conditioned medium of mouse fibroblast L929 cells. J Biol Chem 1984;259(17):10978–82PubMedGoogle Scholar
  65. 65.
    Stahl J, Gearing DP, Willson TA, Brown MA, King JA, Gough NM. Structural organization of the genes for murine and human leukemia inhibitory factor. Evolutionary conservation of coding and non-coding regions. J Biol Chem 1990;265(15):8833–41PubMedGoogle Scholar
  66. 66.
    Gascan H, Godard A, Ferenz C, Naulet J, Praloran V, Peyrat MA, Hewick R, Jacques Y, Moreau JF, Soulillou JP. Characterization and amino-terminal aminoacid sequence of natural human interleukin of DA cells/leukemia inhibitory factor. J Biol Chem 1989;264:21509–15PubMedGoogle Scholar
  67. 67.
    Rathjen PD, Toth S, Willis A, Heath JK, Smith AG. Differentiation inhibiting activity is produced in matrix-associated and diffusible forms that are generated by alternate promoter usage. Cell 1990;62(6):1105–14CrossRefPubMedGoogle Scholar
  68. 68.
    Turnley AM, Bartlett PF. Cytokines that signal through the leukemia inhibitory factor receptor-(beta) complex in the nervous system. J Neurochem, 2000;74:889–99CrossRefPubMedGoogle Scholar
  69. 69.
    Gearing DP, Thut CJ, VandeBos T, Gimpel SD, Delaney PB, King J, Price V, Cosman D, Beckmann MP. Leukemia inhibitory factor receptor is structurally related to the IL-6 signal transducer, gp130. EMBO J 1991;10:2839–48PubMedGoogle Scholar
  70. 70.
    Gearing DP, Bruce AG. Oncostatin M binds the high-affinity leukemia inhibitory factor receptor. New Biol 1992;4:61–65PubMedGoogle Scholar
  71. 71.
    Davis S, Aldrich TH, Valenzuela DM, Wong VV, Furth ME, Squinto SP, Yancopoulos GD. The receptor for ciliary neurotrophic factor. Science 1991;253:59–63PubMedGoogle Scholar
  72. 72.
    Stahl N, Yancopoulos GD. Thr tripartite CNTF receptor complex: activation and signalling involve components shared with other cytokines. J Neurobiol 1994;25:1454–66CrossRefPubMedGoogle Scholar
  73. 73.
    Metcalf D, Hilton D, Nicola NA. Leukemia inhibitory factor can potentiate murine megakaryocyte production in vitro. Blood 1991;77(10):2150–53PubMedGoogle Scholar
  74. 74.
    Murray R, Lee F, Chiu CP. The genes for leukemia inhibitory factor and interleukin-6 are expressed in mouse blastocysts prior to the onset of hemopoiesis. Mol Cell Biol 1990;10(9):4953–56PubMedGoogle Scholar
  75. 75.
    Barto JL, Nathanson NM. Differential regulation of leukemia inhibitory factor-stimulated neuronal gene expression by protein phosphatases SHP-1 and SHP-2 through mitogen-activated protein kinase-dependent and-independent pathways. J Neurochem 2000;74(5):2021–32Google Scholar
  76. 76.
    Zhong Z, Wen Z, Darnell JE Jr. Stat3: a STAT family member activated by tyrosine phosphorylation in response to epidermal growth factor and interleukin-6. Science 1994;264:95–98PubMedGoogle Scholar
  77. 77.
    Ware CB, Horowitz Md, Renshaw BR, Hunt JS, Liggitt D, Koblar SA, Gliniak BC, McKenna HJ, Papayannopoulou T, Thoma B, Cheng L, Donovan PJ, Peschon JJ, Bartlett PF, Willis CR, Wright BD, Carpenter MK, Davison BL, Gearing DP. Targeted disruption of the low-affinity leukemia inhibitory factor receptor gene causes placental, skeletal, neural and metabolic defects and results in perinatal death. Development 1995;121:1283–99PubMedGoogle Scholar
  78. 78.
    Heath JK, Smith AG, Hsu LW, Rathjen PD. Growth and differentiation factors of pluripotential stem cells. J Cell Sci Suppl 1990;13:75–85PubMedGoogle Scholar
  79. 79.
    Vogiagis D, Salamonsen LA. Review: The role of leukaemia inhibitory factor in the establishment of pregnancy. J Endocrinol 1999; 160(2): 181–90CrossRefPubMedGoogle Scholar
  80. 80.
    Escary JL, Perreau J, Dumenil D, Ezine S, Brulet P. Leukaemia inhibitory factor is necessary for maintenance of haematopoietic stem cells and thymocyte stimulation. Nature 1993; 363:361–64CrossRefPubMedGoogle Scholar
  81. 81.
    Stewart CL, Kaspar P, Brunet LJ, Bhatt H, Gadi I, Kontgen F, Abbondanzo SJ. Blastocyst implantation depends on maternal expression of leukaemia inhibitory factor. Nature 1992;359:76–79CrossRefPubMedGoogle Scholar
  82. 82.
    Yue ZP, Yang ZM, Wei P, Li SJ, Wang HB, Tan JH, Harper MJ. Leukemia inhibitory factor, leukemia inhibitory factor receptro, and glycoprotein 130 in rhesus monkey uterus during menstrual cycle and early pregnancy. Biol Reprod 2000;63(2);508–12CrossRefPubMedGoogle Scholar
  83. 83.
    Passavant C, Zhao X, Das SK, Dey SK, Mead RA. Changes in uterine expression of leukemia inhibitory factor receptor gene during pregnancy and its Up-regulation by prolactin in the western spotted skunk. Biol Reprod 2000;636(1):301–07Google Scholar
  84. 84.
    Piccinni MP, Maggi E, Romagnani S. Role of hormone-controlled T-cell cytokines in the maintenance of pregnancy. Biochem Soc Trans 2000;28(2):212–15PubMedGoogle Scholar
  85. 85.
    Hsieh YY, Tsai HD, Chang CC, Hsu LW, Chang SC, Lo HY. Prolonged culture of human cryopreserved embryos with recombinant human leukemia inhibitory factor. J Assist Reprod Genet 2000;17(3):131–34PubMedGoogle Scholar
  86. 86.
    Martin TJ, Allan EH, Evely RS, Reid IR. Leukaemia inhibitory factor and bone cell function. Ciba Foundation Symposium 1992;167:141–50PubMedGoogle Scholar
  87. 87.
    Cornish J, Gallon K, King A, Edgar S, Reid IR. The effect of leukemia inhibitory factor on bone in vivo. Endocrinology. 1993;132(3):1359–66CrossRefPubMedGoogle Scholar
  88. 88.
    Malaval L, Gupta AK, Aubin JE. Leukemia inhibitory factor inhibits osteogenic differentiation in rat calvaria cell cultures. Endocrinology. 1995;136(4):1411–18CrossRefPubMedGoogle Scholar
  89. 89.
    Chandrasekhar S, Harvey AK. Modulation of PDGF mediated osteoblast chemmotaxis by leukemia inhibitory factor (LIF). J Cell Physiol 1996;169(3):481–90CrossRefPubMedGoogle Scholar
  90. 90.
    Sabokbar A, Fujikawa Y, Brett J, Murray DW, Athanasou NA. Increased osteoclastic differentiation by PMMA particle-associated macrophages. Inhibitory effect by interleukin 4 and leukemia inhibitory factor. Acta Orthopaedica Scandinavica 1996;67(6):593–98PubMedGoogle Scholar
  91. 91.
    Malaval L, Gupta AK, Liu F, Delmas PD, Aubin JE. LIF, but IL-6, regulates osteoprogenitor differentiation in rat calvaria cell cultures: modulation by dexamethasone. J Bone Miner Res 1998;13(2):175–84PubMedGoogle Scholar
  92. 92.
    Bohic S, Rohanizadeh R, Touchais S, Godard A, Daculsi G, Heymann D. Leukemia inhibitory factor and oncostatin M influence the mineral phases formed in a murine heterotopic calcification model: a Fourier transform-infrared microspectroscopic study. J Bone Miner Res 1998;13(10):1619–32PubMedGoogle Scholar
  93. 93.
    Thomson BM, Saklatvala J, Chambers TJ. Osteoblasts mediate interleukin 1 stimulation of bone resorption by rat osteoclasts. J Exp Med 1986;164(1):104–12CrossRefPubMedGoogle Scholar
  94. 94.
    Thomson BM, Mundy GR, Chambers TJ. Tumor necrosis factors alpha and beta induce osteoblastic cells to stimulate osteoclastic bone resorption. J Immunol 1987;138(3):775–79PubMedGoogle Scholar
  95. 95.
    Beutler B, Cerami A. Cachectin: more than a tumor necrosis factor. N Engl J Med 1987;316(7):379–85PubMedGoogle Scholar
  96. 96.
    Beutler BA, Cerami A. Recombinant interleukin 1 suppresses lipoprotein lipase activity in 3T3-L1 cells. J Immunol 1985;135(6):3969–71PubMedGoogle Scholar
  97. 97.
    Metcalf D. Disease states induced by hemopoietic growth factor excess: their implications in medicine. Int J Cell Cloning 1990; 8 Suppl 1: 374–87; discussion 387–90PubMedGoogle Scholar
  98. 98.
    Gadient RA, Patterson PH. Leukemia inhibitory factor, Interleukin 6, and other cytokines using the GP130 transducing receptor: roles in inflammation and injury. Stem Cells 1999;17(3):127–37PubMedGoogle Scholar
  99. 99.
    Brown MA, Metcalf D, Gough NM. Leukaemia inhibitory factor and interleukin 6 are expressed at very low levels in the normal adult mouse and are induced by inflammation. Cytokine 1994:6:300–09CrossRefPubMedGoogle Scholar
  100. 100.
    Block MI, Berg M, McNamara MJ. Passive immunization of mice against D factor blocks lethality and cytokine release during endotoxemia. J Exp Med 1993;178:1085–90CrossRefPubMedGoogle Scholar
  101. 101.
    Alexander HR, Wong GG, Doherty GM. Differentiation factor/leukemia inhibitory factor protection against lethal endotoxemia inmice: synergistic effect with interleukin 1 and tumor necrosis factor. J Exp Med 1992; 175:1139–42CrossRefPubMedGoogle Scholar
  102. 102.
    Waring PM, Waring LJ, Billington T. Leukemia inhibitory factor protects against experimental lethal Escherichia coli septic shock in mice. Proc Natl Acad Sci USA 1995;92:1337–41PubMedGoogle Scholar
  103. 103.
    Carroll G, Bell M, Wang H. Antagonism of the IL-6 cytokine subfamily—a potential strategy for more effective therapy in rheumatoid arthritis. Inflamm Res 1998;47:1–7CrossRefPubMedGoogle Scholar
  104. 104.
    Hui W, Bell M, Carroll G. Oncostatin M (OSM) stimulates resorption and inhibits synthesis of proteoglycan in porcine articular cartilage explants. Cytokine 1996;8:495–00CrossRefPubMedGoogle Scholar
  105. 105.
    Lotz M, Moats T, Villiger PM. Leukeamia inhibitory factor is expressed in cartilage and synovium and can contribute to the pathogenesis of arthritis. J Clin Invest 1992;90:888–96PubMedGoogle Scholar
  106. 106.
    Okamoto H, Yamamura M, Morita Y. The synovial expression and serum levels of interleukin-6, interleukin-11, leukemia inhibitory factor, and oncostatin M in rheumatoid arthritis. Arthritis Rheum 1997;40:1096–05PubMedGoogle Scholar
  107. 107.
    Waring PM, Carroll GJ, Kandiah DA. Increased levels of leukemia inhibitory factory in synovial fluid from patients with rheumatoid arthritis and other inflammatory arthritides. Arthritis Rheum 1993;36:911–15PubMedGoogle Scholar
  108. 108.
    Henrotin YE, De GD, Labasse AH. Effects of exogenous IL-1 beta, TNF alpha, IL-6, IL-8 and LIF on cytokine production by human articular chondrocytes. Osteoarth Cart 1996;4:163–73Google Scholar
  109. 109.
    Chabaud M, Fossiez F, Taupin JL. Enhancing effect of IL-17 on IL-1-induced IL-6 and leukemia inhibitory factor production by rheumatoid arthritis synoviocytes and its regulation by Th2 cytokines. J Immunol 1998;161:409–14PubMedGoogle Scholar
  110. 110.
    Bell M, Carroll GJ, Chapman H. Leukemia inhibitory factor (LIF) binding protein attenuates the phlogistic and abolishes the chondral effects of LIF in goat joints. J Rheumatol 1997;24:2394–02PubMedGoogle Scholar
  111. 111.
    Heymann D, Her E, Nguyen JM. Leukaemia inhibitory factor (LIF) production in pleural effusions: comparison with production of IL-4, IL-8, IL-10 and macrophage-colony stimulating factor (M-CSF). Cytokine 1996;410–16Google Scholar
  112. 112.
    Jorens PG, De JR, Bossaert LL. High levels of leukaemia inhibitory factor in ARDS. Cytokine 1996;8:873–76CrossRefPubMedGoogle Scholar
  113. 113.
    Szepietowski JC, McKenzie RC, Keohane SG. Leukaemia inhibitory factor: induction in the early phase of allergic contact dermatitis. Contact Dermatitis 1997; 36:21–25PubMedGoogle Scholar
  114. 114.
    McKenzie RC, Paglia D, Kondo S. A novel endogenous mediator or cutaneous inflammation: leukemia inhibitory factor. Acta Derm Venerol 1996;76:111–14PubMedGoogle Scholar
  115. 115.
    Thompson SW, Dray A, Urban L. Leukemia inhibitory factor induces mechanical allodynia but not thermal hyperalgesia in the juvenile rat. Neuroscience 1996;71:1091–94CrossRefPubMedGoogle Scholar
  116. 116.
    Banner LR, Patterson pH, Allchorne A. Leukemia inhibitory factor is an anti-inflammatory and analgesic cytokine. J Neurosci 1998;18:5456–62PubMedGoogle Scholar
  117. 117.
    Banner LR, Patterson PH. Major changes in the expression of the mRNAs for cholinergic differentiation factor/leukemia inhibitory factor and its receptor after injury to adult peripheral nerves and ganlia. Proc Natl Acad Sci USA 1994;91:7109–13PubMedGoogle Scholar
  118. 118.
    Banner LR, Moayeri NN, Patterson PH. Leukemia inhibitory factory is expressed in astrocytes following corticla brain injury. Exp Neurol 1997;147:1–9CrossRefPubMedGoogle Scholar
  119. 119.
    Curtis R, Scherer SS, Somogyi R. Retrograde axonal trnsport of LIF is increased by peripheral nerve injury: correlation with increased LIF expression in distal nerve. Neuron 1994;12:191–04CrossRefPubMedGoogle Scholar
  120. 120.
    Kurek JB, Ausin L, Cheema SS. Upregulation of eukaemia inhibitory factor and interleukin-6 in transected sciatic nerve and musce following denervation. Neuromuscul Disord 1996;6:105–14PubMedGoogle Scholar
  121. 121.
    Kurek JB, Austin L, Cheema SS, Bartlett PF, Murphy M. Upregulation of leukaemia inhibitory factor and interleukin-6 in transected sciatic nerve and denervated muscle. Neuromusc Disor 1996;6:105–14Google Scholar
  122. 122.
    Austin L, Burgess AW. Stimulation of myoblast proliferation in culture by leukaemia inhibitory factor. J Neurol Sci 1991;101:193–97CrossRefPubMedGoogle Scholar
  123. 123.
    Austin L, Bower J, Kurek J, Vakakis N. Effects of leukaemia inhibitory factor and other cytokines on murine and human myoblast proliferation. J Neurol Sci 1992;112:185–91CrossRefPubMedGoogle Scholar
  124. 124.
    Patterson PH, Kou S-Y, Sugiura S. LIF coordinates neuronal and inflammatory response to nerve injury. Soc Neurosci Abstr 1997;23:393–33Google Scholar
  125. 125.
    Baumann H, Jahreis GP, Sauder DN, Koj A. Human keratinocytes and monocytes release factors which regulate the synthesis of major acute phase plasma proteins in hepatic cells from man, rat, and mouse. J Biol Chem 1984;259(11):7331–42PubMedGoogle Scholar
  126. 126.
    Kordula T, Rokita H, Koj A. Effects of interleukin-6 and leukemia inhibitory factor on the acute phase response and DNA synthesis in cultured rat hepatocytes. Lymphokine Cytokine Res 1991:10:23–26PubMedGoogle Scholar
  127. 127.
    Mayer P, Geissler K, Ward M. Recombinant human leukemia inhibitory factor induces acute phase proteins and raises the blood platelet counts in nonhuman primates. Blood 1993;81:3226–33PubMedGoogle Scholar
  128. 128.
    Richards LJ, Kilpatrick TJ, Dutton R, Tan S-S, Gearing DP, Bartlett PF, Murphy M. Leukaemia inhibitory factor (LIF) and related factors promote the differentiation of neuronal and astrycytic precursors within the developing murine spinal cord. Eur J Neurosci 1996;8:291–99PubMedGoogle Scholar
  129. 129.
    Li M, Sendtner M, Smith A. Essential function of LIF receptor in motor neurones. Nature 1995;378:724–27PubMedGoogle Scholar
  130. 130.
    Cheema SS, Richards LR, Murphy M, Bartlett PF. Leukemia inhibitory factor rescues motorneurones from axotomy-induced cell death. Neuroreport 1994;5:989–92PubMedGoogle Scholar
  131. 131.
    Ikeda K, Iwasaki Y, Shiojima T, Kinoshita M. Neuroprotective effect of cholinergic differentiation leukaemia inhibitory factor on Wobbler murine motor neurone disease. Muscle Nerve 1995:18:1344–47PubMedGoogle Scholar
  132. 132.
    Metcalf D. The induction and inhibition of differentiation in normal and leukaemic cells. Philos Trans R Soc Lond B Biol Sci 1990;327(1239):99–109.PubMedGoogle Scholar
  133. 133.
    Shabo Y, Lotem J, Rubinstein M, Revel M, Clark SC, Wolf SF, et al. The myeloid blood cell differentiation-inducing protein MGI-2A is interleukin-6. Blood 1988;72(6):2070–73PubMedGoogle Scholar
  134. 134.
    Metcalf D. Suppression of myeloid leukemic cells by normal hemopoietic regulators. Recent Prog Cytokine Res 1989;10:11–19Google Scholar
  135. 135.
    Maekawa T, Metcalf D. Clonal suppression of HL60 and U937 cells by recombinant human leukemia inhibitory factor in combination with GM-CSF or G-CSF. Leukemia 1989;3(4):270–76PubMedGoogle Scholar
  136. 136.
    Maekawa T, Metcalf D, Gearing DP. Enhanced suppression of human myeloid leukemic cell lines by combinations of IL-6, LIF, GM-CSF and G-CSF. Int J Cancer 1990;45(2):353–58PubMedGoogle Scholar
  137. 137.
    Wang C, Lishner M, Minden MD, McCulloch EA. The effects of leukemia inhibitory factor (LIF) on the blast stem cells of acute myeloblastic leukemia. Leukemia 1990;4(8):548–52PubMedGoogle Scholar
  138. 138.
    Metcalf D, Hilton DJ, Nicola NA. Clonal analysis of the actions of the murine leukemia inhibitory factor on leukemic and normal murine hemopoietic cells. Leukemia 1988;2(4):216–21PubMedGoogle Scholar
  139. 139.
    Leary AG, Wong GG, Clark SC, Smith AG, Ogawa M. Leukemia inhibitory factor differentiation-inhibiting activity/human interleukin for DA cells augments proliferation of human hematopoietic stem cells. Blood 1990;75(10):1960–64PubMedGoogle Scholar
  140. 140.
    Verfaillie C, McGlave P. Leukemia inhibitory factor/human interleukin for DA cells: a growth factor that stimulates the in vitro development of multipotential human hematopoietic progenitors. Blood 1991;77(2):263–70PubMedGoogle Scholar
  141. 141.
    Estrov Z, Talpaz M, Wetzler M, Kurzrock R. The modulatory hematopoietic activities of leukemia inhibitory factor. Leuk Lymphoma 1992;8(1–2):1–7PubMedGoogle Scholar
  142. 142.
    Wetzler M, Kurzrock R, Lowe DG, Kantarjian H, Gutterman JU, Talpaz M. Alteration in bone marrow adherent layer growth factor expression: a novel mechanism of chronic myelogenous leukemia progression. Blood 1991;78(9):2400–06PubMedGoogle Scholar
  143. 143.
    Shen MM, Skoda RC, Cardiff RD, Campos-Torres J, Leder P, Orntiz DM. Expression of LIF in transgenic mice results in altered thymic epitehlium and apparent interconversion of thymic and lymph node morphologies. EMBO J 1994;1375–85Google Scholar
  144. 144.
    Schaafsma MR, Falkenburg JH, Duinkerken N, Moreau JF, Soulillou JP, Willemze R, Fibbe WE. Human interleukin for DA cells (HILDA) does not affect the proliferation and differentiation of hematopoietic progenitor cells in human long-term bone marrow cultures. Exp Hematol 1992;20:6–10PubMedGoogle Scholar
  145. 145.
    Firkin FC, Birner R, Farag S. Differential action of diffusible molecules in long-term bone marrow culture on proliferation of leukaemic and normal haemopoietic cells. Br J Haematol 1993;84:8–15PubMedGoogle Scholar
  146. 146.
    Debili N, Masse JM, Katz A, Guichard J, Breton-Gorius J, Vainchenker W. Effects of the recombinant hematopoietic growth factors intermegakayocytic differentiation of CD34+ cells. Blood 1993;82:84–95PubMedGoogle Scholar
  147. 147.
    Gabutti V, Timeus F, Ramenghi U, Crescenzio N, Marranca D, Miniero R, Cornaglia G, Bagnara GP. Expansion of cord blood progenitors and use for hemopoietic reconstitution. Stem Cells 1993;11 Suppl: 105–12PubMedGoogle Scholar
  148. 148.
    Szilvassy SJ, Cory S. Efficient retroviral gene transfer to purified long-term repopulating hematopoietic stem cells. Blood 1994;84:74–83PubMedGoogle Scholar
  149. 149.
    Szilvassy SJ, Weller K.P, Kin W, Sharma AK, Ho AS, Tsukamoto A, Hoffman R, Leiby KR, Gearing DP. Leukemia inhibitory factor upregulates cytokine expression by a murine stromal cell line enabling the maintenance of highly enriched competitive repopulating stem cells. Blood 1996;87:4618–28PubMedGoogle Scholar
  150. 150.
    Metcalf D. Leukemia inhibitory factor — a puzzling poly-functional regulator. Growth Factors 1992; 7:169–73PubMedGoogle Scholar
  151. 151.
    Kamohara H, Sakamoto K, Ishiko T, Masuda Y, Abe T, Ogawa M. Leukemia inhibitory factor induces apoptosis and proliferation of human carcinoma cells through different oncogene pathways. Int J Cancer 1997;72(4):687–95CrossRefPubMedGoogle Scholar
  152. 152.
    Moreau JF, Bonneville M, Peyart MA, Jacques Y, Soulillou JP. Capactiy of alloreactive human T clones to produce factor(s) inducing proliferation of the IL3-dependent DA-1 murine cell line. I. Evidence that this production is under IL2 control. Ann Inst Pasteur Immunol 1986; 137C(1):25–37PubMedGoogle Scholar
  153. 153.
    Abe T, Murakami M, Sato T, Kajiki M, Ohno M, Kodaira R. Macrophage differentiation inducing factor from human monocytic cells is equivalent to murine leukemia inhibitory factor. J Biol Chem 1989;264:8941PubMedGoogle Scholar
  154. 154.
    Xie P, Chan FS, Ip NY, Leung MF. Induction of gp130 and LIF by differentiation inducers in human myeloid leukemia K562 cells. Leuk Res 1999;23(12):1113–19CrossRefPubMedGoogle Scholar
  155. 155.
    Wetzler M, Estrov Z, Talpaz M, Kim KJ, Alphonso M, Srinivasan R, Kurzrock R. Leukemia inhibitory factor in long-term adherent layer cultures: increased levels of bioactive protein in leukemia and modulation by IL-4, IL-Iß and TNF-α Cancer Res 1994; 54:1837–42PubMedGoogle Scholar
  156. 156.
    Maekawa T, Metcalf D, Gearing DP. Enhanced suppression of human myeloid leukemic cell lines by combinations of IL-6, LIF, GM-CSF and G-CSF. Int J Cancer 1990;45(2):353–58PubMedGoogle Scholar
  157. 157.
    Yamamoto-Yamaguchi Y, Tomida M, Hozumi M. Prolongation by differentiation-stimulating factor/leukemia inhibitory factor of the survival time of mice implanted with mouse myeloid leukemia cells. Leuk Res 1992;16(10):1025–29CrossRefPubMedGoogle Scholar
  158. 158.
    Godard A, Heymann D, Raher S, Anegon I, Peyrat MA, Le Mauff B, Mouray E, Gregoire M, Virdee K, Soulillou JP et al. High and low affinity receptors for human interleukin for DA cells/leukemia inhibitory factor on human cells. Molecular characterization and cellular distribution. J Biol Chem 1992;267(36):3214–22PubMedGoogle Scholar
  159. 159.
    Umemiya-Okada T, Natazuka T, Matsui T, Ito M, Taniguchi T, Nakao Y. Expression and regulation of the leukemia inhibitory factor/D factor gene in human T-cell leukemia virus type 1 infected T-cell lines. Cancer Res 1992;52(24):6961–65PubMedGoogle Scholar
  160. 160.
    Lal RB, Rudolph D, Buckner C, Pardi D, Hooper WC. Infection with human T-lymphotropic viruses leads to constitutive expression ofleukemia inhibitory factor and interleukin-6. Blood 1993;81(7):1827–32PubMedGoogle Scholar
  161. 161.
    Gu ZJ, Zhang XG, Hallet MM, Lu ZY, Wijdenes J, Rossi JF, Klein B. A ciliary neurotrophic factor-sensitive human myeloma cell line. Exp Hematol 1996;24:1195–00PubMedGoogle Scholar
  162. 162.
    Portier M, Zhang XG, Ursule E, Lees D, Jourdan M, Bataille R, Klein B. Cytokine gene expression inhumanmultiple myeloma. Br J Haematol 1993; 85:514–20PubMedGoogle Scholar
  163. 163.
    Nishimoto N, Ogata A, Shima Y, Tani Y, Ogawa H, Nakagawa M, Sugiyama H, Yoshizaki K, Kishimoto T. Oncostain M, leukemia inhibitory factor, and interleukin 6 induce the proliferation of human plasmacytoma cells via the common signal transducer, gp130. J Exp Med 1994;179(4): 1343–47CrossRefPubMedGoogle Scholar
  164. 164.
    Zhang XG, Gu JJ, Lu ZY, Yasukawa K, Yancopoulos GD, Turner K, Shoyab M, Taga T, Kishimoto T, Bataille R. et al. Ciliary neurotropic factor, interleukin 11, leukemia inhibitory factor, and oncostatin M are growth factors for human myeloma cell lines using the interleukin 6 signal transducer gp130. Institute for Molecular Genetics, CNRS BP5051, Montepellier, France.Google Scholar
  165. 165.
    Marusic A, Kalinowski JF, Jastrzebski S, Lorenzo JA. Production of leukemia inhibitory factor mRNA and protein by malignant and immortalized bone cells. J Bone Miner Res 1993;8(5):617–24PubMedGoogle Scholar
  166. 166.
    Gouin F, Heymann D, Raher S, DeGroote D, Passuti N, Daculsi G, Godard A. Increased levels of leukaemia inhibitory factor (LIF) in urine and tissue culture supernatant from human primary bone tumors. Cytokine 1998;10(2):110–14CrossRefPubMedGoogle Scholar
  167. 167.
    Soueidan A, Gan OL, Gouin F, Godard A, Heymann D, Jacques Y, Daculsi G. Culturing of cells fromg iant cell tumour of boneon natural and synthetic calcified substrata: the effect of leukaemia inhibitory factor and vitamin D3 on the resorbing activity of osteoclast-like cells. Virchows Archiv 1995;426(5):469–77CrossRefPubMedGoogle Scholar
  168. 168.
    Gouin F, Couillaud S, Cottrel M, Godard A, Passuti N, Heymann D. Presence of leukaemia inhibitory factor (LIF) and LIF-receptor chain (gp190) in osteoclast-like cells cultured from human giant cell tumour of bone. Ultrastructural distribution. Cytokine 1999;11(4):282–89CrossRefPubMedGoogle Scholar
  169. 169.
    Estrov Z, Samal B, Lapushin R, Kellokumpu-Lehitinen P, Sahin AA, Kurzrock R, Talpaz M, Aggarwal BB. Leukemia inhibitory factor binds to human breast cancer cells and stimulates their proliferation. J Interferon Cytokine Res 1995;156(10):905–13Google Scholar
  170. 170.
    Kellokumpu-Lehtinen P, Talpaz M, Harris D, Van Q, Kurzrock R, Estrov Z. Leukemia-inhibitory factor stimulates breast, kidney and prostate cancer cell proliferation by paracrine and autocrine pathways. Int J Cancer 1996;66(4):515–19CrossRefPubMedGoogle Scholar
  171. 171.
    Liu J, Hadjokas N, Mosley B, Estrov Z, Spence MJ, Vestal RE. Oncostatin M-spccific receptor expression and function in regulating cell proliferation of normal and malignant mammary epithelial. Cytokine 1998;10(4):295–02CrossRefPubMedGoogle Scholar
  172. 172.
    Douglas AM, Goss GA, Sutherland RL, Hilton DJ, Berndt MC, Nicola NA, Begley CG. Expression and function of members of the cytokine receptorsuper family on breast cancer cells. Oncogene 1997;14(6):661–69CrossRefPubMedGoogle Scholar
  173. 173.
    Dhingra K, Sahin A, Emami K, Hortobagyi GN, Estrov Z. Expression of leukemia inhibitory factor and its receptor in breast cancer: a potential autocrine and paracrine growth regulatory mechanism. Breast Cancer Res Treat 1998;48(2):165–74CrossRefPubMedGoogle Scholar
  174. 174.
    Crichton MB, Nichols JE, Zhao Y, Bulun SE, Simpson ER. Expression of transcripts of interleukin-6 and related cytokines by human breast tumors, breast cancer cells, and adipose stromal cells. Cell Endocrinol 1996;120(2):215Google Scholar
  175. 175.
    Tatoud R, Desgrandchamps F, Gegeorges A, Thomas F. Peptide growth factors in the prostate. Pathol Biol 1993; 41:731–40PubMedGoogle Scholar
  176. 176.
    Mori M, Yamaguchi K, Honda S, Nagasaki K, Ueda M, Abe O, Abe K. Cancer cachexia syndrome developed in nude mice bearing melanoma cells producing leukemia-inhibitory factor. Cancer Res 1991;51(24):6656–59PubMedGoogle Scholar
  177. 177.
    Paglia D, Oran A, Lu C, Kerbel RS, Sauder DN, McKenzie RC. Expression of leukemia inhibitory factor and interleukin-11 by human melanoma cell lines: LIF, IL-6, and IL-11 arr not coregulated. J Interferon Cytokine Res 1995;15(5):455–60PubMedGoogle Scholar
  178. 178.
    Heymann D, Godard A, Raher S, Ringeard S, Lassort D, Blanchard F, Harb J. Human interleukin for DA cells/leukemia inhibitory factor and oncostatin M enhance membrane expression of intercellular adhesion molecule-1 on melanoma cells but not the shedding of its soluble form. Cytokine 1995;7(2):111CrossRefPubMedGoogle Scholar
  179. 179.
    Kamobara H, Sakamoto K, Ishiko T, Mita S, Masuda Y, Abe T, Ogawa M. Human carcinoma cell lines produce biologically active leukemia inhibitory factor (LIF). Res Commun Mol Pathol Pharmacol 1994Google Scholar
  180. 180.
    Baumann H, Ziegler SF, Mosley B, Morella KK, Pajovic S, Gearing DP. Reconstitution of the response to leukemia inhibitory factor, oncostatin M, and ciliary neurotrophic factor in hepatoma cells. J Biol Chem 1993;268(12):8414–17PubMedGoogle Scholar
  181. 181.
    Hermanns HM, Radtke S, Haan C, Schmitz-Van de Leur H, Tavernier J, Heinrich PC, Behrmann I. Contributions of leukemia inhibitory factor receptor and oncostatin M receptor to signal transduction in heterodimeric complexes with glycoprotein 130. J Immunol 1999;163(12):6651–58PubMedGoogle Scholar
  182. 182.
    Guimbaud R, Abitbol V, Bertrand V, Quartier G, Chauvelot-Moachon L, Giroud J, Couturier D, Chaussade DC. Leukemia inhibitory factor involvement in human ulcerative colitis and its potential role in malignant course. Eur Cytokine Netw 1998;9(4):607–12PubMedGoogle Scholar
  183. 183.
    Halfter H, Kremerskothen J, Weber J, Hacker-Klom U, Barnekow A, Ringelstein EB, Stogbauer F. Growth inhibition of newly established human glioma cell lines by leukemia inhibitory factor. J Neuro Oncol 1998, 39(1):1–18CrossRefGoogle Scholar
  184. 184.
    Halfter H, Lotfi R, Westermann R, Young P, Ringelstein EB, Stogbauer FT. Inhibition of growth and induction of differentiation of glioma cell lines by oncostatin M (OSM). Growth Factors 1998;15(2):135–47PubMedGoogle Scholar
  185. 185.
    Liu J, Li H, Moreau JF. Expression of LIF as autocrinal growth factor in human medulloblastomas. Chung Hua Ping Li Hsueh Tsa Chih 1996;25(l):24–26PubMedGoogle Scholar
  186. 186.
    Liu J, Li H, Hamou MF. Inhibitory effect of antisense LIF oligonucleotide on the outgrowth of human medulloblastoma cells. Chung Hua Ping Li Hsueh Tsa Chih 1996;25(3):132–34PubMedGoogle Scholar
  187. 187.
    Fu J, Zheng J, Fang W, Wu B. Effect of interleukin-6 on the growth of human lung cancer cell line. Chin Med J 1998;111(3):265–68PubMedGoogle Scholar
  188. 188.
    Kajimura N, Iseki H, Tanaka R, Ohue C, Otsubo K, Gyoutoku M, Sasaki K, Akiyama Y, Yamaguchi K. Toxohormones responsible for cancer cachexia syndrome in nude mice bearing human cancer cell lines. Cancer Chemother Pharmacol 1996;38 Suppl:S48–52CrossRefGoogle Scholar
  189. 189.
    Bamberger AM, Jenatschke S, Erdmann I, Schulte HM. Progestin-dependent stimulation of the human leukemia inhibitory factor promoter in SKUT-1B uterine tumor cells. J Reprod Immunol 1997;33(3):189–01PubMedGoogle Scholar
  190. 190.
    Tomida M. Presence of mRNAs encoding the soluble D-factor/LIF receptor in human choriocarcinoma cells and production of the soluble receptor. Biochem Biophys Res Commun 1997;232(2):427–31CrossRefPubMedGoogle Scholar
  191. 191.
    Voyle RB, Haines BP, Pera MF, Forrest R, Rathjen PD. Human germ cell tumor cell lines express novel leukemia inhibitory factor transcripts encoding differentially localized proteins. Exp Cell Res 1999;249(2):199–11CrossRefPubMedGoogle Scholar
  192. 192.
    Shabo Y, Lotem J, Rubinstein M, Revel M, Clark SC, Wolf SF, Kamen R, Sachs L. The myeloid blood cell differentiation-inducing protein MG1-2A is interleukin-6. Blood 1988; 72:2070–73PubMedGoogle Scholar
  193. 193.
    Keller JR, Gooya JM, Ruscetti FW. Direct synergistic effects of leukemia inhibitory factor on hematopoietic progenitor cell growth: comparison with other hematopoietins that use the gp130 receptor subunit. Blood 1996;88(3):863–69PubMedGoogle Scholar
  194. 194.
    Heymann D, Gouin F, Guicheux J, Munevar JC, Godard A, Daculsi G. Upmodulation of multinucleated cell formation in long-term human bone marrow cultures by leukaemia inhibitory factor. Cytokine 1997;9(l):46–52PubMedGoogle Scholar
  195. 195.
    Zucman J, Delattre O, Desmaze C, Plougastel B, Joubert I, Melot T, Peter M, De Jong P, Rouleau G, Aurias A. et al. Cloning and characterization of the Ewing’s sarcoma and peripheral neuroepithelioma t(11;22) translocation breakpoints. Genes Chromosome Cancer 1992;5(4):271–77Google Scholar
  196. 196.
    Mansi JL, Berger U, McDonnell T, Pople A, Rayter Z, Gazet JC, Coombes RC. The fate of bone marrow micrometastases in patients with primary breast cancer. J Clin Oncol 1989;7:445–49PubMedGoogle Scholar
  197. 197.
    Akatsu T, Ono K, Katayama Y, Tamura T, Nishikawa M, Kugai N, Yamamoto M, Nagata N. The mouse mammary tumor cell line, MMT060562, produces prostaglandin E2 and leukemia inhibitory factor and supports osteoclast formation in vitro via a stromal cell-dependent pathway. J Bone Miner Res 1998;13(3):400–08PubMedGoogle Scholar
  198. 198.
    Bamberger AM, Thuneke I, Schulte HM. Differential regulation of the human ‘leukemia inhibitory factor’ (LIF) promoter in T47D and MDA-MB231 breast cancer cells. Breast Cancer Res Treat 1998;47(2):153–61CrossRefPubMedGoogle Scholar
  199. 199.
    Bard JB, Ross AS. LIF, the ES-cell inhibition factor, reversibly blocks nephrogenesis in cultured mouse kidney rudiments. Development 1991;113(l):193–98PubMedGoogle Scholar
  200. 200.
    Hartner A, Sterzel BR, Reindi N, Hocke GM, Fey GH, Gopplet-Struebe M. Cytokine-induced expression of leukemia inhibitory factor in renal mesangial cells. Kidney Int 1994;45:1562–71PubMedGoogle Scholar
  201. 201.
    Gleave ME, Hsieh JT, von Eschenbach AC, Chung LW. Prostate and bone fibroblasts induce human prostate cancer growth in vivo: implications for bidirectional tumor-stromal cell implication in prostate carcinoma growth and metastasis. J Urol 1992;147:1151–59PubMedGoogle Scholar
  202. 202.
    Hirano T, Matsuda T, Nakajima K. Signal transduction through gp130 that is shared among the receptors for the interleukin 6 related subfamily. Stem Cells 1994;12:262–77PubMedGoogle Scholar
  203. 203.
    Chung TD, Yu JJ, Spiotto MY, Bartkowski M, Simons JW. Characterization of the role of IL-6 in the progression of prostate cancer. Prostate 1999;38:199–207CrossRefPubMedGoogle Scholar
  204. 204.
    Mori S, Murakami-Mori K, Bonavida B. Oncostatin M (OM) promotes the growth of DU 145 human prostate cancer cells, but not PC-3 or LNCaP, through the signaling of the OM specific receptor. Anticancer Res 1999;19:1011–5PubMedGoogle Scholar
  205. 205.
    Heymann D, Blanchard F, Raher S, DeGroote D, Godard A. Modulation of LIF expression in human melanoma cells by oncostatin M. Immunol Lett 1995;46(3):245–51CrossRefPubMedGoogle Scholar
  206. 206.
    Schrell UM, Koch HU, Marschalek R, Schrauzer T, Anders M, Adams E, Fahlbusch R. Formation of autocrine loops in human cerebral meningioma tissue by leukemia inhibitor factor, interleukin-6, and oncostatin M: inhibition of meningioma cell growth in vitro by recombinant oncostatin M. J Neurosurg 1998,88(3):541–48PubMedGoogle Scholar
  207. 207.
    Knight DA, Lydell CP, Zhou D, Weir TD, Schellenberg R, Bai TR. Leukemia inhibitory factor (LIF) and LIF receptor in human lung. Distribution and regulation of LIF release. Am J Respir Cell Mol Biol 1999;20(4);834–41PubMedGoogle Scholar
  208. 208.
    Freidin M, Kessler JA. Cytokine regulation of substance P expression in sympathetic neurons. Proc Natl Acad Sci U S A 1991;88(8):3200–03PubMedGoogle Scholar
  209. 209.
    Murphy M, Reid K, Hilton DJ, Bartlett PF. Generation of sensory neurones is stimulated by leukaemia inhibitory factor. Proc Natl Acad Sci USA 1991;88:3498–01PubMedGoogle Scholar
  210. 210.
    Yamakuni H, Minami M, Satoh M. Localisation of mRNA for leukaemia inhibitory factor receptor in the adult brain. J Neuroimmunol 1996;70:45–43CrossRefPubMedGoogle Scholar
  211. 211.
    Cheema SS, Richards L, Murphy M, Bartlett PF. Leukemia inhibitory factor prevents the death of axotomised sensory neurones in the dorsal root ganglion of the neonatal rat. J Neurosci Res 1994;37:213–18CrossRefPubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 2001

Authors and Affiliations

  • Farhad Ravandi
    • 1
  • Zeev Estrov
    • 1
  1. 1.Department of BioimmunotherapyThe University of Cancer CenterHoustonUSA

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