Skip to main content
SpringerLink
Log in

Transforming growth factor-ßs as modulators of pericellular proteolytic events

  • Published:
Cytotechnology Aims and scope Submit manuscript

Abstract

Since the discovery of transforming growth factor-ß:s an increasing number of different biological effects have been attributed to this group of proteins. Analysis of the cellular responses to TGFß stimulation at the molecular level has indicated that TGFß acts as an activator of transcription of several genes. This may in part explain the plethora of various functions that have been ascribed to TGFß. In addition to the TGFß family of polypeptides there is an increasing number of related factors, whose major roles appear to be involved in developmental processes. A distinct feature of TGFß is its ability to regulate pericellular proteolysis of cultured cells. As yet this property has not been associated with other members of this group of polypeptides. Depending on the target cell type TGFß may either increase or decrease pericellular proteolytic activity. Proteolytic activation of latent TGFß and its possible inhibition by TGFß-induced protease inhibitors could be a physiological feed-back mechanism in the control of proteolytic activity in the vicinity of cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

GM-CSF:

Granulocyte-Monocyte Colony Stimulating Factor

EGF:

Epidermal Growth Factor

IL:

Interleukin

MIS:

Müllerian Inhibitory Substance

NGF:

Nerve Growth Factor

PA:

Plasminogen Activator

PAI:

Plasminogen Activator Inhibitor

PAI-1:

Endothelial-type (type-1) Plasminogen Activator Inhibitor

PAI-2:

Placental-type (type-2) Plasminogen Activator Inhibitor

PDGF:

Platelet Derived Growth Factor

TGFα:

Transforming Growth Factor-α

TGFß:

Transforming Growth Factor-ß

t-PA:

Tissue-type Plasminogen Activator

u-PA:

Urokinase-type Plasminogen Activator

References

  1. Andreasen PA, Nielsen LS, Kristensen P, Grøndahl-Hansen J, Skriver L and Danø K (1986) Plasminogen activator inhibitor from human fibrosarcoma cells binds urokinasetype plasminogen activator, but not its proenzyme. J. Biol. Chem. 261: 7644–7651.

    Google Scholar 

  2. Anzano MA, Roberts AB, Meyers CA, Komoriya A, Lamb LC, Smith JM and Sporn MB (1982) Synergistic interaction of two classes of transforming growth factors from murine sarcoma cells. Cancer Res. 42: 4776–4778.

    Google Scholar 

  3. Anzano MA, Roberts AB, Smith JM, Lamb LC and Sporn MB (1982) Purification by reverse-phase high-performance liquid chromatography of an epidermal growth factor-dependent transforming growth factor. Anal. Biochem. 125: 217–224.

    Google Scholar 

  4. Anzano MA, Roberts AB, Smith JM, Sporn MB and DeLarco JE (1983) Sarcoma growth factor from conditioned medium of virally transformed cells is composed of both type α and type-ß transforming growth factors. Proc. Natl. Acad. Sci. USA 80: 6264–6268.

    Google Scholar 

  5. Assoian RK, Grotendorst GR, Miller DM and Sporn MB (1984) Cellular transformation by coordinated action of three peptide growth factors from human platelets. Nature 309: 804–806.

    Google Scholar 

  6. Assoian RK, Komoriya A, Meyers CA, Miller DM and Sporn MB (1983) Transforming growth factor-ß in human platelets. Identification of a major storage site, purification, and characterization. J. Biol. Chem. 258: 7155–7160.

    Google Scholar 

  7. Cate RL, Mattaliano RJ, Hession C, Tizard R, Farber NM, Cheung A, Ninfa EG, Frey AZ, Gash DJ, Chow EB, Fisher RA, Bertonis JM, Torres G, Wallner BP, Ramachandran KL, Ragin RC, Manganaro TF, MacLaughlin DT and Donahoe PK (1986) Isolation of the bovine and human genes for Müllerian inhibiting substance and expression of the human gene in animal cells. Cell 45: 685–698.

    Google Scholar 

  8. Cheifetz S, Weatherbee JA, Tsang ML-S, Anderson JK, Mole JE, Lucas R and Massagué J (1987) The transforming growth factor-ß system, a complex pattern of cross-reactive ligands and receptors. Cell 48: 409–415.

    Google Scholar 

  9. Chen J-M and Chen W-T (1987) Fibronectin-degrading proteases from the membranes of transformed cells. Cell 48: 193–203.

    Google Scholar 

  10. Chiang C-P and Nilsen-Hamilton M (1986) Opposite and selective effects of epidermal growth factor and human platelet transforming growth factor-ß on the production of secreted proteins by murine 3T3 cells and human fibroblasts. J. Biol. Chem. 261: 10478–10481.

    Google Scholar 

  11. Childs CB, Proper JA, Tucker RF and Moses HL (1982) Serum contains a platelet-derived transforming growth factor. Proc. Natl. Acad. Sci. USA 79: 5312–5316.

    Google Scholar 

  12. Chua CC, Geiman DE, Keller GH and Ladda RL (1985) Induction of collagenase secretion in human fibroblast cultures by growth promoting factors. J. Biol. Chem. 260: 5213–5216.

    Google Scholar 

  13. Coffey RJJr., Kost LJ, Lyons RM, Moses HL and LaRusso NF (1987) Hepatic processing of transforming growth factor-ß in the rat. Uptake, metabolism, and biliary excretion. J. Clin. Invest. 80: 750–757.

    Google Scholar 

  14. Danø K, Andreasen PA, Grøndahl-Hansen J, Kristensen P, Nielsen LS and Skriver L (1985) Plasminogen activators, tissue degradation, and cancer. Adv. Cancer Res. 44: 139–266.

    Google Scholar 

  15. Davies RL, Rifkin DB, Tepper R, Miller A and Kucherlapati R (1983) A polypeptide secreted by transformed cells that modulates human plasminogen activator production. Science 221: 171–173.

    Google Scholar 

  16. de Martin R, Haendler B, Hofer-Warbinek R, Gaugitsch H, Schlüsener H, Seifert JM, Bodmer S, Fontana A and Hofer E (1987) Complementary DNA for human glioblastomaderived T cell suppressor factor, a novel member of the transforming growth factor-ß gene family. EMBO J. 6: 3676–3677.

    Google Scholar 

  17. DeLarco JE and Todaro GJ (1987) Growth factors from murine sarcoma virus-transformed cells. Proc. Natl. Acad. Sci. USA 75: 4001–4005.

    Google Scholar 

  18. Denhardt DT, Hamilton RT, Parfett CLJ, Edwards DR St. Pierre R, Waterhouse P and Nilsen-Hamilton M (1986) Close relationship of the major exreted protein of transformed murine fibroblasts to thiol-dependent cathepsins. Cancer Res. 46: 4590–4593.

    Google Scholar 

  19. Derynck R, Jarrett JA, Chen EY, Eaton DH, Bell JR, Assoian RK, Roberts AB, Sporn MB and Goeddel DV (1985) Human transforming growth factor-ß complementary DNA sequence and expression in normal and transformed cells. Nature 316: 701–705.

    Google Scholar 

  20. Derynck R, Jarrett JA, Chen EY and Goeddel DV (1986) The murine transforming growth factor fl precursor. J. Biol. Chem. 251: 4377–4379.

    Google Scholar 

  21. Derynck R, Goeddel DV, Ullrich A, Gutterman JU, Williams RD, Bringman TS and Berger WH (1987) Synthesis of messenger RNAs for transforming growth factors α and ß and the epidermal growth factor receptor by human tumors. Cancer Res. 47: 707–712.

    Google Scholar 

  22. Derynck R, Lindquist PB, Lee A, Wen D, Tamm J, Graycar JL, Rhee L, Mason AJ, Miller DA, Coffey RJ, Moses HL, and Chen EY (1988) A new type of transforming growth factor, TGF-ß3. EMBO J. 7: 3737–3743.

    Google Scholar 

  23. Eaton DL and Baker JB (1983) Phorbol esters and mitogens stimulate human fibroblast secretions of plasmin-activatable plasminogen activator and protease nexin, an antiactivator/antiplasmin. J. Cell Biol. 97: 323–328.

    Google Scholar 

  24. Edwards DR, Parfett CLJ and Denhardt DT (1985) Transcriptional regulation of two serum-induced RNAs in mouse fibroblasts: Equivalence of one species to 132 repetitive elements. Mol. Cell. Biol. 5: 3280–3288.

    Google Scholar 

  25. Edwards DR, Murphy G, Reynolds JJ, Whitham SE, Docherty AJP, Angel P, and Heath JK (1987) Transforming growth factor-ß modulates the expression of collagenase and metalloproteinase inhibitor. EMBO J. 6: 1899–1904.

    Google Scholar 

  26. Erickson LA, Ginsberg MH and Loskutoff DJ (1984) Detection and partial characterization of an inhibitor of plasminogen activator in human platelets. J. Clin. Invest. 74: 1465–1472.

    Google Scholar 

  27. Fairbairn S, Gilbert R, Ojakian G, Schwimmer R and Quigley JP (1965) The extracellular matrix of normal chick embryo fibroblasts: Its effect on transformed chick fibroblasts and its proteolytic degradation by the transformants. J. Cell Biol. 101: 1790–1796.

    Google Scholar 

  28. Florini JR, Roberts AB, Ewton DZ, Falen SL, Flanders KC and Sporn MB (1986) Transforming growth factor-ß: A very potent inhibitor of myoblast differentiation, identical to the differentiation inhibitor secreted by buffalo rat liver cells. J. Biol. Chem. 261: 16509–16513.

    Google Scholar 

  29. Frolik CA, Dart LL, Meyers CA, Smith DM and Sporn MB (1983) Purification and initial characterization of a type-ß transforming growth factor from human placenta. Proc. Natl. Acad. Sci. USA 80: 3676–3680.

    Google Scholar 

  30. Gentry LE, Webb NR, Lim GJ, Brunner AM, Ranchalis JE, Twardzik DR, Lioubin MN, Marquardt H and Purchio AF (1987) Type 1 transforming growth factor-ß: amplified expression and secretion of mature and precursor polypeptide in Chinese hamster ovary cells. Mol. Cell. Biol. 7: 4318–4327.

    Google Scholar 

  31. Gerwin BI, Keski-Oja J, Seddon M, Lechner JF and Harris CC (1989) Differential modulation by TGFß1 of the expression of urokinase and type-1 plasminogen activator inhibitor in normal and squamous differentiation-defective human bronchial epithelial cells. J. Cell. Physiol. (submitted).

  32. Gold LI, Schwimmer R, Rostagno A and Quigley JP (1989) Human plasma fibronectin as a substrate for human urokinase. Biochem. J. (in press)

  33. Gottesman MM (1978) Transformation-dependent secretion of a low molecular weight protein by murine fibroblasts. Proc. Natl. Acad. Sci. USA 75: 2767–2771.

    Google Scholar 

  34. Hanks SK, Armour R, Baldwin JH, Maldonado F, Spiess J and Holley RW (1988) Amino acid sequence of the BSC-1 cell growth inhibitor (polyergin) deduced from the nucleotide sequence of the cDNA. Proc. Natl. Acad. Sci. USA 85: 79–82.

    Google Scholar 

  35. Hekman CM and Loskutoff DJ (1985) Endothelial cells produce a latent inhibitor of plasminogen activators that can be activated by denaturants. J. Biol. Chem. 260: 11581–11587.

    Google Scholar 

  36. Holley RW, Armour R and Baldwin JH (1978) Density-dependent regulation of growth of BSC-1 cells in cell culture: Growth inhibitors formed by the cells. Proc. Natl. Acad. Sci. USA 75: 1864–1866.

    Google Scholar 

  37. Holley RW, Böhlen P, Fava R, Baldwin JH, Kleeman G and Armour R (1980) Purification of kidney epithelial cell growth inhibitors. Proc. Natl. Acad. Sc. USA 77: 5989–5992.

    Google Scholar 

  38. Huang JS, Huang SS and Deuel TF (1984) Specific covalent binding of platelet derived growth factor to human plasma α2-macroglobulin. Proc. Natl. Acad. Sci. USA 81: 342–346.

    Google Scholar 

  39. Huang SS, O'Grady P and Huang JS (1988) Human transforming growth 329-2 complex is a latent form of transforming growth factor-ß-α2-macroglobulin complex is a latent form of transforming growth factor-ß. J. Biol. Chem. 263: 1535–1541.

    Google Scholar 

  40. Hurme M, Sihvola M, Alitalo K and Keski-Oja J (1989) Transforming growth factor-ß does not alter interleukin-1 expression in cultured human macrophages. J. Cell. Biochem. 39: 467–475.

    Google Scholar 

  41. Ignotz RA and Massagué J (1985) Type-ß transforming growth factor controls the adipogenic differentiation of 3T3 fibroblasts. Proc. Natl. Acad. Sci. USA 82: 8530–8534.

    Google Scholar 

  42. Ignotz RA and Massagué J (1986) Transforming growth factor-ß stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix. J. Biol. Chem. 261: 4337–4345.

    Google Scholar 

  43. Jakowlew SBm Dillard PJ, Sporn MB and Roberts AB (1988) Complementary Deoxyribonucleic Acid Cloning of a Messenger Ribonucleic Acid Encoding Transforming Growth Factor-ß4 From Chicken Embryo Chondrocytes. Mol. Endocrinol. (in press)

  44. Josso N, Picard J-Y and Tran D (1977) The antimüllerian hormone. Recent Prog. Horm. Res. 33: 117–158.

    Google Scholar 

  45. Keski-Oja J and Todaro GJ (1980) Specific effects of fibronectin-releasing peptides on the extracellular matrices of cultured human fibroblasts. Cancer Res. 40: 4722–4727.

    Google Scholar 

  46. Keski-Oja J and Vaheri A (1982) The cellular target for the plasminogen activator urokinase, in human fibroblasts-66.000 dalton protein. Biochim. Biophys. Acta 720: 141–146.

    Google Scholar 

  47. Keski-Oja J, Leof EB, Lyons RM, Coffey RJ and Moses HL (1987) Transforming growth factors and control of neoplastic cell growth. J. Cell. Biochem. 33: 95–107.

    Google Scholar 

  48. Keski-Oja J, Blasi F, Leof EB and Moses HL (1988) Regulation of the synthesis and activity of urokinase plasminogen activator in A549 human lung carcinoma cells by transforming growth factor-ß. J. Cell Biol. 106: 451–459.

    Google Scholar 

  49. Keski-Oja J, Postlethwaite AE and Moses HL (1988) Transforming growth factors in the regulation of malignant cell growth and invasion. Cancer Invest. 6: 705–724.

    Google Scholar 

  50. Keski-Oja J, Raghow R, Sawdey M, Loskutoff DJ, Postlethwaite AE, Kang AH and Moses HL (1988) Regulation of mRNAs for type-1 plasminogen activator inhibitor, fibronectin and type 1 procollagen by transforming growth factor-ß: Divergent responses in lung fibroblasts and carcinoma cells. J. Biol. Chem. 263: 3111–31115.

    Google Scholar 

  51. Keski-Oja J, Laiho M and Lohi J (1989) Activation of latent cell-derived transforming growth factor-ß by the plasminogen activator urokinase. J. Cell. Biol. 107, (pt. 3): 50a.

    Google Scholar 

  52. Keski-Oja J and Vartio T (1989) Pericellular substrate for urokinase is a gelatin degrading enzyme that is enhanced by transforming growth factor-ß. J. Cell. Biol. 109 (pt. 2). (in press)

    Google Scholar 

  53. Kimelman D and Kirschner M (1987) Synergistic induction of mesoderm by FGF and TGFß and the identification of an mRNA coding for FGF in the early Xenopus embryo. Cell 51: 869–877.

    Google Scholar 

  54. Knudsen BS, Harpel PC and Nachman RL (1987) Plasminogen activator inhibitor is associated with the extracellular matrix of cultured bovine smooth muscle cells. J. Clin. Invest. 80: 1082–1089.

    Google Scholar 

  55. Kooistra T, Sprengers ED and van Hinsbergh VWM (1986) Rapid inactivation of the plasminogen activator inhibitor upon secretion from cultured human endothelial cells. Biochem. J. 239: 497–503.

    Google Scholar 

  56. Kryceve-Martinerie C, Lawrence DA, Crochet J, Jullien P and Vigier P (1985) Further study of ß-TGFs released by virally transformed and non-transformed cells. Int. J. Cancer. 35: 553–558.

    Google Scholar 

  57. Laiho M, Saksela O and Keski-Oja J (1986) Transforming growth factor-ß alters plasminogen activator activity in human skin fibroblasts. Exp. Cell Res. 164: 399–407.

    Google Scholar 

  58. Laiho M, Saksela O, Andreasen PA and Keski-Oja J (1986) Enhanced production and extracellular deposition of the endothelial-type plasminogen activator inhibitor in cultured human lung fibroblasts by transforming growth factor-ß. J. Cell Biol. 103: 2403–2410.

    Google Scholar 

  59. Laiho M, Saksela O and Keski-Oja J (1987) Transforming growth factor-ß induction of type-1 plasminogen activator inhibitor. Pericellular deposition and sensitivity to exogenous urokinase. J. Biol. Chem. 262: 17467–17474.

    Google Scholar 

  60. Laiho M (1988) Modulation of extracellular proteolytic activity and anchorage-independent growth of cultured cells by sarcoma cell-derived factors. Relationships to transforming growth factor-ß. Exp. Cell Res. 176: 297–308.

    Google Scholar 

  61. Laiho M (1988) Transforming growth factor-ß in the regulation of extracellular proteolysis of cultured cells. Thesis. University of Helsinki, Helsinki, Finland.

    Google Scholar 

  62. Laiho M and Keski-Oja J (1989) Growth factors in the regulation of extracellular proteolysis: A review. Cancer Res. 49: 2533–2553.

    Google Scholar 

  63. Lawrence DA, Pircher R, Kryceve-Martinerie C and Jullien P (1984) Normal embryo fibroblasts release transforming growth factors in a latent form. J. Cell. Physiol. 121: 184–188.

    Google Scholar 

  64. Lawrence DA, Pircher R and Jullien P (1985) Conversion of a high molecular weight latent ß-TGF from chicken embryo fibroblasts into a low molecular weight active ß-TGF under acidic conditions. Biochem. Biophys. Res. Commun. 133: 1026–1034.

    Google Scholar 

  65. Levin EG (1983) Latent tissue plasminogen activator produced by human endothelial cells in culture: Evidence for an enzyme-inhibitor complex. Proc. Natl. Acad. Sci. USA 80: 6804–6808.

    Google Scholar 

  66. Levin EG (1986) Quantitation and properties of the active and latent plasminogen activator inhibitors in cultures of human endothelial cells. Blood 67: 1309–1313.

    Google Scholar 

  67. Levin EG and Santell L (1987) Association of a plasminogen activator inhibitor (PAI-1) with the growth substratum and membrane of human endothelial cells. J. Cell Biol. 105: 2543–2549.

    Google Scholar 

  68. Liotta LA, Tryggyason K, Garbisa S, Hart I, Foltz CM and Shafie S (1980) Metastatic potential correlates with enzymatic degradation of basement membrane collagen. Nature 284: 67–68.

    Google Scholar 

  69. Lohi J, Pertovaara L, Sistonen L, Alitalo K and Keski-Oja J (1989) Regulation by TGFß of genes involved in growth control: interleukin-6. Ann. N.Y. Acad. Sci., submitted.

  70. Lund LR, Riccio A, Andreasen PA, Nielsen LS, Kristensen P, Laiho M, Saksela O, Blasi F and Danø K (1987) Transforming growth factor-ß is a strong and fast acting positive regulator of the level of type-1 plasminogen activator inhibitor mRNA in WI-38 human lung fibroblasts. EMBO J. 6: 1281–1286.

    Google Scholar 

  71. Lyons RM, Gentry LE, Purchio AF and Moses HL (1989) Proteolytic processing and activation of latent transforming growth factor-ß. J. Cell. Biol. 107, (pt. 3): 51 a.

    Google Scholar 

  72. Lyons RM, Keski-Oja J and Moses HL (1988) Proteolytic activation of latent transforming growth factor-ß from fibroblast conditioned medium. J. Cell. Biol. 106: 1659–1665.

    Google Scholar 

  73. Machida CM, Muldoon LL, Rodland KD and Magun BE (1988) Transcriptional modulation of transin gene expression by epidermal growth factor and transforming growth factor-ß. Mol. Cell. Biol. 8: 2479–2483.

    Google Scholar 

  74. Madisen L, Webb T, Rose TM, Marquardt H, Ikeda T, Twardzik D, Seyedin S and Purchio AF (1988) Transforming growth factor-ß2: cDNA cloning and sequence analysis. DNA 7: 1–8.

    Google Scholar 

  75. Marquardt H, Lioubin MN and Ikeda T (1987) Complete amino acid sequence of human transforming growth factor type ß2. J. Biol. Chem. 262: 12127–12131.

    Google Scholar 

  76. Mason AJ, Hayflick JS, Ling N, Esch F, Ueno N, Ying S-Y, Guillemin R, Niall H and Seeburg PH (1985) Complementary DNA sequences of ovarian follicular fluid inhibin show precursor structure and homology with transforming growth factor-ß. Nature 318: 659–663

    Google Scholar 

  77. Massagué J, Cheifetz S, Endo T and Nadal-Ginard B (1986) Type-ß transforming growth factor is an inhibitor of myogenic differentiation. Proc. Natl. Acad. Sci. USA 83: 8206–8210.

    Google Scholar 

  78. Massagué J (1987) The TGF-ß family of growth and differentiation factors. Cell 49: 437–438.

    Google Scholar 

  79. Masui T, Wakefield LM, Lechner JF, La Veck MA, Sporn MB and Harris CC (1986) Type-ß transforming growth factor is the primary differentiation-inducing serum factor for normal human bronchial epithelial cells. Proc. Natl. Acad. Sci. USA 83: 2438–2442.

    Google Scholar 

  80. Matrisian LM, Glaichenhaus N, Gesnel M-C and Breathnach R (1985) Epidermal growth factor and oncogenes induce transcription of the same cellular mRNA in rat fibroblasts. EMBO J. 4: 1435–1440.

    Google Scholar 

  81. Matrisian LM, Leroy P, Ruhlmann C, Gesnel M-C and Breathnach R (1986) Isolation of the oncogene and epidermal growth factor-induced transin gene: complex control in rat fibroblasts. Mol. Cell. Biol. 6: 1679–1686.

    Google Scholar 

  82. Mignatti P, Robbins E and Rifkin DB (1986) Tumor invasion through the human amniotic membrane: Requirement for a proteinase cascade. Cell 47: 487–498.

    Google Scholar 

  83. Mimuro J, Schleef RR and Loskutoff DJ (1987) Extracellular matrix of cultured bovine aortic endothelial cells contains functionally active type 1 plasminogen activator inhibitor. Blood 70: 721–728.

    Google Scholar 

  84. Miyazono K, Hellman U, Wernstedt C and Heldin C-H (1988) Latent high molecular weight complex of transforming growth factor-ß1. Purification from human platelets and structural characterization. J. Biol. Chem. 263: 6407–6415.

    Google Scholar 

  85. Miyazono K and Heldin CH (1989) Role for carbohydrate structures in TGF-ß1 latency Nature 338: 158–160.

    Google Scholar 

  86. Moses HL, Branum EB, Proper JA and Robinson RA (1981) Transforming growth factor production by chemically transformed cells. Cancer Res. 41: 2842–2848.

    Google Scholar 

  87. Moses HL, Tucker RF, Leof EB, Coffey RJJ, Halper J and Shipley GD (1985) Type-ß transforming growth factor is a growth stimulator and a growth inhibitor. In: ‘Cancer Cells’ (eds. J. Feramisco, B. Ozanne and C. Stiles) Cold Spring Harbor Press, New York, vol. 3, pp. 65–75.

    Google Scholar 

  88. Mullins DE and Rorlich ST (1983) The role of proteinases in cellular invasiveness. Biochim. Biophys. Acta 695: 177–214.

    Google Scholar 

  89. Newman MJ, Lane EA, Nugent MA and Racker E (1986) Induction of anchorage-independent growth by epidermal growth factor and altered sensitivity to type-ß transforming growth factor in partially transformed rat kidney cells. Cancer Res. 46: 5842–5850.

    Google Scholar 

  90. Newman M, Lane EA, Iannotti A, Nugent MA, Pepinsky RB and Keski-Oja J (1989) Characterization and purification of a plasminogen activator inhibitor induced in normal rat kidney cells by transforming growth factor-ß. J. Biol. Chem., submitted.

  91. Nilsen-Hamilton M and Holley RW (1983) Rapid selective effects by a growth inhibitor and epidermal factor on the incorporation of [35S]methionine into proteins secreted by African green monkey (BSC-1) cells. Proc. Natl. Acad. Sc. USA 80: 5636–5640.

    Google Scholar 

  92. Nugent MA, Lane EA, Keski-Oja J, Moses HL and Newman MJ (1989) Growth stimulation, altered regulation of high affinity epidermal growth factor receptors, and autocrine transformation in spontaneously transformed normal rat kidney cells by transforming growth factor-ß. Cancer Res. 49: 3884–3890.

    Google Scholar 

  93. O'Connor-McCourt MD and Wakefield LM (1987) Latent transforming growth factor-ß in serum: A specific complex with α2-macroglobulin. J. Biol. Chem. 262: 14090–14099.

    Google Scholar 

  94. O'Grady RL, Upfold LI and Stephens RW (1981) Rat mammary carcinoma cells secrete active collagenase and activate latent enzyme in the stroma via plasminogen activator. Int. J. Cancer 28: 509–515.

    Google Scholar 

  95. Ohta M, Greenberg JS, Anklesaria P, Bassols A and Massagué J (1987) Two forms of transforming growth factor-ß distinguished by multipotential haematopoietic progenitor cells. Nature 329: 539–541.

    Google Scholar 

  96. Ossowski L and Reich E (1983) Antibodies to plasminogen activator inhibit human tumor metastasis. Cell 35: 611–619.

    Google Scholar 

  97. Overall CM, Wrana JL and Sodek J (1989) Independent regulation of collagenase, 72-kDa progelatinase, and metalloendoproteinase inhibitor expression in human fibroblasts by transforming growth factor-\. J. Biol. Chem. 264: 1860–1869.

    Google Scholar 

  98. Padgett RW, St. Johnston RD and Gelbart WM (1987) A transcript from a Drosophila pattern gene predicts a protein homologous to the transforming growth factor-\ family. Nature 325: 81–84.

    Google Scholar 

  99. Pepinsky RB, Sinclair LK, Chow EP, Mattaliano RJ, Manganaro TF, Donahoe PK and Cate RL (1988) Proteolytic processing of Müllerian inhibiting substance produces a transforming growth factor-\ like fragment. J. Biol. Chem. 263: 18961–18964.

    Google Scholar 

  100. Pertovaara L, Sistonen L, Bos TJ, Vogt PK, Keski-Oja J and Alitalo K (1989) Enhanced jun gene expression is an early genomic response to transforming growth factor-\ stimulation. Mol. Cell. Biol. 9: 1255–1262.

    Google Scholar 

  101. Piersbacher MD and Ruoslahti E (1984) Variants of the cell recognition site of fibronectin that retain attachment promoting activity. Proc. Natl. Acad. Sci. USA 81: 5985–5988.

    Google Scholar 

  102. Pircher R, Jullien P and Lawrence DA (1986) \-transforming growth factor is stored in human blood platelets as a latent high molecular weight complex. Biochem. Biophys. Res. Commun. 136: 30–37.

    Google Scholar 

  103. Postlethwaite AE, Keski-Oja J, Moses HL and Kang AH (1987) Stimulation of the chemotactic migration of human fibroblasts by transforming growth factor-\. J. Exp. Med. 165: 251–256.

    Google Scholar 

  104. Quigley JP (1976) Association of a protease (plasminogen activator) with a specific membrane fraction isolated from transformed cells. J. Cell Biol. 71: 472–486.

    Google Scholar 

  105. Quigley JP, Goldfarb RH, Scheiner C, O'Donnel-Tormey J and Yeo TK (1980) Plasminogen activator and the membrane of transformed cells. In: ‘Tumor cell surfaces and malignancy’ (eds. R.O. Hynes, and C.F. Fox), Progress in Clinical and Biological Research, Alan R. Liss Inc., New York, vol. 41, pp. 773–795.

    Google Scholar 

  106. Quigley JP, Gold LI, Schwimmer R and Sullivan L (1987) Limited cleavage of cellular fibronectin by plasminogen activator purified from transformed cells. Proc. Natl. Acad. Sci. USA 84: 2776–2780.

    Google Scholar 

  107. Ricco A, Lund LR, Sartorio R, Lania A, Andreasen PA, Dan∅ K and Blasi F (1988) The regulatory region of the human plaminogen activator inhibitor type-1 (PAI-1) gene. Nucl. Acid Res. 16: 2805–2824.

    Google Scholar 

  108. Rizzino A (1988) Transforming Growth Factor-\: Multiple effects on cell differentiation and extracellular matrices. Dev. Biol. 130: 411–422.

    Google Scholar 

  109. Roberts AB, Anzano MA, Lamb LC, Smith JM and Sporn MB (1981) New class of transforming growth factors potentiated by epidermal growth factor: Isolation from non-neoplastic tissues. Proc. Natl. Acad. Sci. USA 78: 5339–5343.

    Google Scholar 

  110. Roberts AB, Anzano MA, Lamb LC, Smith JM, Frolik CA, Marquardt H, Todaro GJ and Sporn MB (1982) Isolation from murine sarcoma cells of a new class of transforming growth factors potentiated by epidermal growth factor. Nature 295: 417–419.

    Google Scholar 

  111. Roberts AB, Anzano MA, Meyers CA, Wideman J, Blacher R, Pan Y-CE, Stein S, Lehrman SR, Smith LC, Lamb LC and Sporn MB (1983) Purification and properties of a type-\ transforming growth factor from bovine kidney. Biochemistry 22: 5692–5698.

    Google Scholar 

  112. Roberts AB, Sporn MB, Assoian RK, Smith JM, Roche NS, Wakefield LM, Heine UI, Liotta LA, Falanga V, Kehrl JH and Fauci AS (1986) Transforming growth factor type-\: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc. Natl. Acad. Sci. USA 83: 4167–4171.

    Google Scholar 

  113. Ronne H, Anundi H, Rask L and Peterson PA (1979) Nerve growth factor binds to serum alpha2-macroglobulin. Biochem. Biophys. Res. Commun. 87: 330–336.

    Google Scholar 

  114. Rosa F, Roberts AB, Danielpour D, Dart LL Sporn MB and Dawid IB (1988) Mesoderm induction in amphibians: The role of TGF\2-like factors. Science 239: 783–785.

    Google Scholar 

  115. Rossi P, Karsenty G, Roberts AB, Roche NS, Sporn MB and de Crombrugghe B (1988) A nuclear factor 1 binding site mediates the reanscriptional activation of a type 1 collagen promoter by transforming growth factor\. Cell 52: 405–414.

    Google Scholar 

  116. Saksela O, Laiho M and Keski-Oja J (1985) Regulation of plasminogen activator activity in human fibroblastic cells by fibrosarcoma cell-derived factors. Cancer Res. 45: 2314–2319.

    Google Scholar 

  117. Saksela O, Moscatelli D and Rifkin DB (1987) The opposing effects of basic fibroblast growth factor and transforming growth factor-\ on the regulation of plasminogen activator activity in capillary endothelial cells. J. Cell Biol. 105: 957–963.

    Google Scholar 

  118. Saksela O (1985) Plasminogen activation and regulation of pericellular proteolysis. Biochim. Biophys. Acta 823: 35–65.

    Google Scholar 

  119. Salo T, Liotta LA, Keski-Oja J, Turpeenniemi-Hujannen T and Tryggvason K (1982) Secretion of basement membrane collagen degrading enzyme and plasminogen activator by transformed cells-role in metastasis. Int. J. Cancer 30: 669–673.

    Google Scholar 

  120. Scher W (1987) The role of extracellular proteases in cell proliferation and differentiation. Lab. Invest. 57: 607–633.

    Google Scholar 

  121. Seyedin SM, Thomas TC, Thompson AY, Rosen DM and Piez KA (1985) Purification and characterization of two cartilage-inducing factors from bovine demineralized bone. Proc. Natl. Acad. Sci. USA 82: 2267–2271.

    Google Scholar 

  122. Seyedin SM, Thompson AY, Bentz H, Rosen DM, McPherson JM, Conti A, Siegel NR, Galluppi GR and Piez KA (1986) Cartilage-inducing factor-A: Apparent identity to transforming growth factor-\. J. Biol. Chem. 261: 5693–5695.

    Google Scholar 

  123. Seyedin SM, Segarini PR, Rosen DM, Thompson AY, Bentz H and Graycar J (1987) Cartilage-inducing factor-B is a unique protein structurally and functionally related to transforming growth factor\. J. Biol. Chem. 262: 1946–1949.

    Google Scholar 

  124. Sporn MB, Roberts AB, Shull JH, Smith JM, Ward JM and Sodek J (1983) Polypeptide transforming growth factors isolated from bovine sources and used for wound healing in vivo. Science 219: 1329–1331.

    Google Scholar 

  125. Sprengers ED and Kluft C (1987) Plasminogen activator inhibitors. Blood 69: 381–387.

    Google Scholar 

  126. Stoppelli MP, Tacchetti C, Cubellis MV, Corti A, Hearing VJ, Cassani G, Appella E and Blasi F (1986) Autocrine saturation of pro-urokinase receptors on human A431 cells. Cell 45: 675–684.

    Google Scholar 

  127. ten Dijke P, Hansen P, Iwata KK, Pieler C and Foulkes JG (1988) Identification of another member of the transforming growth factor type-\ gene family. Proc. Natl. Acad. Sci. USA 85: 4715–4719.

    Google Scholar 

  128. Thalacker FW and Nilsen-Hamilton M (1987) Specific induction of secreted proteins by transforming growth factor-\ and 12-0-tetradecanoylphorbol-13-acetate. J. Biol. Chem. 262: 2283–2290.

    Google Scholar 

  129. Thompson NL, Flanders KC, Smith JM, Ellingsworth LR, Roberts AB and Sporn MB (1989) Expression of transforming growth factor-\1 in specific cells and tissues of adult and neonatal mice. J. Cell Biol 108: 661–670.

    Google Scholar 

  130. Todaro GJ, DeLarco JE and Cohen S (1976) Transformation by murine and feline sarcoma viruses specifically blocks binding of epidermal growth factor to cells. Nature 264: 26–31.

    Google Scholar 

  131. Tucker RF, Shipley GD, Moses HL and Holley RW (1984) Growth inhibitor from BSC-1 cells is closely related to the platelet type-\ transforming growth factor. Science 226: 705–707.

    Google Scholar 

  132. Van Obberghen-Schilling E, Roche NS, Flanders KC, Sporn MB and Roberts AB (1988) Transforming growth factor-\1 positively regulates its own expression in normal and transformed cells. J. Biol. Chem. 263: 7741–7746.

    Google Scholar 

  133. Wahl SH, Hunt DA, Wakefield LM, McCartney-Francis N, Wahl LM, Roberts AB and Sporn MB (1987) Transforming growth factor type-\ induces monocyte chemotaxis and growth factor production. Proc. Natl. Acad. Sci. USA 84: 5788–5792.

    Google Scholar 

  134. Wakefield LM, Smith DM, Masui T, Harris CC, and Sporn MB (1987) Distribution and modulation of the cellular receptor for transforming growth factor-\. J. Cell Biol. 105: 965–975.

    Google Scholar 

  135. Weeks DL and Melton DA (1987) A maternal mRNA localized to the vegetal hemisphere in Xenopus eggs codes for a growth factor related to TGF\. Cell 51: 861–867.

    Google Scholar 

  136. Werb Z, Mainardi CL, Vater CA and Harris ED (1977) Endogenous activation of latent collagenase by rheumatoid synovial cells. N. Engl. J. Med. 296: 1017–1023.

    Google Scholar 

  137. Wrann M, Bodmer S, de Martin R, Siepl C, Hofer-Warbinek R, Frei K, Hofer E and Fontana A (1987) T-cell suppressor factor from human glioblastoma cells is a 12.5-kd protein closely related to transforming growth factor-\. EMBO J. 6: 1633–1636.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Virology, University of Helsinki, Haartmaninkatu 3, SF-00290, Helsinki, Finland

    Jorma Keski-Oja & Jouko Lohi

  2. Cell Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, 10021, New York, N.Y., USA

    Marikki Laiho

Authors
  1. Jorma Keski-Oja
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jouko Lohi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marikki Laiho
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Keski-Oja, J., Lohi, J. & Laiho, M. Transforming growth factor-ßs as modulators of pericellular proteolytic events. Cytotechnology 2, 317–332 (1989). https://doi.org/10.1007/BF00364996

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00364996

Key words

Search

Navigation