Annals of Hematology

, Volume 97, Issue 10, pp 1749–1755 | Cite as

Promyelocytic leukemia protein in mesenchymal stem cells is essential for leukemia progression

  • Erika Costa de Alvarenga
  • Walison N. Silva
  • Rebecca Vasconcellos
  • Edgar J. Paredes-Gamero
  • Akiva Mintz
  • Alexander BirbrairEmail author
Review Article


The dynamic interactions between leukemic cells and cells resident within the bone marrow microenvironment are vital for leukemia progression. The lack of detailed knowledge about the cellular and molecular mechanisms involved in this cross-talk restricts the design of effective treatments. Guarnerio et al. (2018) by using state-of-the-art techniques, including sophisticated Cre/loxP technologies in combination with leukemia mouse models, reveal that mesenchymal stem cells via promyelocytic leukemia protein (Pml) maintain leukemic cells in the bone marrow niche. Strikingly, genetic deletion of Pml in mesenchymal stem cells raised survival of leukemic mice under chemotherapeutic treatment. The emerging knowledge from this research provides a novel target in the bone marrow niche for therapeutic benefit in leukemia.


Pml Leukemia Mesenchymal stem cells Niche 


Funding information

Alexander Birbrair is supported by a grant from Instituto Serrapilheira/Serra-1708-15285; a grant from Pró-reitoria de Pesquisa/Universidade Federal de Minas Gerais (PRPq/UFMG) (Edital 05/2016); a grant from National Institute of Science and Technology in Theranostics and Nanobiotechnology (CNPq/CAPES/FAPEMIG, Process No. 465669/2014-0); a grant from FAPEMIG [Rede Mineira de Engenharia de Tecidos e Terapia Celular (REMETTEC, RED-00570-16)]; and a grant from FAPEMIG [Rede De Pesquisa Em Doenças Infecciosas Humanas E Animais Do Estado De Minas Gerais (RED-00313-16)]; Erika Costa de Alvarenga is supported by a grant from FAPEMIG [Rede Mineira de Pesquisa e Inovação para Bioengenharia de Nanosistemas (RED-00282-16)]; Akiva Mintz is supported by the National Institute of Health (1R01CA179072-01A1) and by the American Cancer Society Mentored Research Scholar grant (124443-MRSG-13-121-01-CDD).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Siegel RL, Miller KD, Jemal A (2017) Cancer statistics, 2017. CA Cancer J Clin 67(1):7–30. CrossRefGoogle Scholar
  2. 2.
    Claus R, Lubbert M (2003) Epigenetic targets in hematopoietic malignancies. Oncogene 22(42):6489–6496. CrossRefGoogle Scholar
  3. 3.
    Papaemmanuil E, Gerstung M, Bullinger L, Gaidzik VI, Paschka P, Roberts ND, Potter NE, Heuser M, Thol F, Bolli N, Gundem G, Van Loo P, Martincorena I, Ganly P, Mudie L, McLaren S, O’Meara S, Raine K, Jones DR, Teague JW, Butler AP, Greaves MF, Ganser A, Dohner K, Schlenk RF, Dohner H, Campbell PJ (2016) Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med 374(23):2209–2221. CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Birbrair A (2017) Stem cell microenvironments and beyond. Adv Exp Med Biol 1041:1–3. CrossRefGoogle Scholar
  5. 5.
    Azevedo PO, Paiva AE, Santos GSP, Lousado L, Andreotti JP, Sena IFG, Mintz A, Birbrair A (2018) Cross-talk between lung cancer and bones results in neutrophils that promote tumor progression. Cancer Metastasis RevGoogle Scholar
  6. 6.
    Tabe Y, Konopleva M (2017) Leukemia stem cells microenvironment. Adv Exp Med Biol 1041:19–32. CrossRefGoogle Scholar
  7. 7.
    Konopleva M, Konoplev S, Hu W, Zaritskey AY, Afanasiev BV, Andreeff M (2002) Stromal cells prevent apoptosis of AML cells by up-regulation of anti-apoptotic proteins. Leukemia 16(9):1713–1724. CrossRefGoogle Scholar
  8. 8.
    Birbrair A, Almeida GG, Borges IDT, Gilson Sena IF, da Silva ML, Goncalves R, Mintz A, Delbono O (2017) How plastic are pericytes? Stem Cells Dev 26(14):1013–1019. CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Frenette PS, Pinho S, Lucas D, Scheiermann C (2013) Mesenchymal stem cell: keystone of the hematopoietic stem cell niche and a stepping-stone for regenerative medicine. Annu Rev Immunol 31:285–316. CrossRefGoogle Scholar
  10. 10.
    Pinho S, Lacombe J, Hanoun M, Mizoguchi T, Bruns I, Kunisaki Y, Frenette PS (2013) PDGFRalpha and CD51 mark human nestin+ sphere-forming mesenchymal stem cells capable of hematopoietic progenitor cell expansion. J Exp Med 210(7):1351–1367. CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Asada N, Kunisaki Y, Pierce H, Wang Z, Fernandez NF, Birbrair A, Ma'ayan A, Frenette PS (2017) Differential cytokine contributions of perivascular haematopoietic stem cell niches. Nat Cell Biol 19(3):214–223. CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Khan JA, Mendelson A, Kunisaki Y, Birbrair A, Kou Y, Arnal-Estape A, Pinho S, Ciero P, Nakahara F, Ma’ayan A, Bergman A, Merad M, Frenette PS (2016) Fetal liver hematopoietic stem cell niches associate with portal vessels. Science 351(6269):176–180. CrossRefGoogle Scholar
  13. 13.
    Guarnerio J, Mendez LM, Asada N, Menon AV, Fung J, Berry K, Frenette PS, Ito K, Pandolfi PP (2018) A non-cell-autonomous role for Pml in the maintenance of leukemia from the niche. Nat Commun 9(1):66. CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Almeida VM, Paiva AE, Sena IFG, Mintz A, Magno LAV, Birbrair A (2017) Pericytes make spinal cord breathless after injury. Neuroscientist:107385841773152. CrossRefGoogle Scholar
  15. 15.
    Santos GSP, Prazeres P, Mintz A, Birbrair A (2017) Role of pericytes in the retina. Eye 32:483–486. CrossRefGoogle Scholar
  16. 16.
    Azevedo PO, Sena IFG, Andreotti JP, Carvalho-Tavares J, Alves-Filho JC, Cunha TM, Cunha FQ, Mintz A, Birbrair A (2017) Pericytes modulate myelination in the central nervous system. J Cell PhysiolGoogle Scholar
  17. 17.
    Andreotti JP, Lousado L, Magno LAV, Birbrair A (2017) Hypothalamic neurons take center stage in the neural stem cell niche. Cell Stem Cell 21(3):293–294. CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Sena IFG, Paiva AE, Prazeres PHDM, Azevedo PO, Lousado L, Bhutia SK, Salmina AB, Mintz A, Birbrair A (2018) Glioblastoma-activated pericytes support tumor growth via immunosuppression. Cancer Med 7:1232–1239. CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Greenbaum A, Hsu YM, Day RB, Schuettpelz LG, Christopher MJ, Borgerding JN, Nagasawa T, Link DC (2013) CXCL12 in early mesenchymal progenitors is required for haematopoietic stem-cell maintenance. Nature 495(7440):227–230. CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Krueger KC, Costa MJ, Du H, Feldman BJ (2014) Characterization of Cre recombinase activity for in vivo targeting of adipocyte precursor cells. Stem Cell Rep 3(6):1147–1158. CrossRefGoogle Scholar
  21. 21.
    Logan M, Martin JF, Nagy A, Lobe C, Olson EN, Tabin CJ (2002) Expression of Cre recombinase in the developing mouse limb bud driven by a Prxl enhancer. Genesis 33(2):77–80. CrossRefGoogle Scholar
  22. 22.
    Martin JF, Bradley A, Olson EN (1995) The paired-like homeo box gene MHox is required for early events of skeletogenesis in multiple lineages. Genes Dev 9(10):1237–1249CrossRefGoogle Scholar
  23. 23.
    Kawanami A, Matsushita T, Chan YY, Murakami S (2009) Mice expressing GFP and CreER in osteochondro progenitor cells in the periosteum. Biochem Biophys Res Commun 386(3):477–482. CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop D, Horwitz E (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8(4):315–317. CrossRefGoogle Scholar
  25. 25.
    Pereira LX, Viana CTR, Orellano LAA, Almeida SA, Vasconcelos AC, Goes AM, Birbrair A, Andrade SP, Campos PP (2017) Synthetic matrix of polyether-polyurethane as a biological platform for pancreatic regeneration. Life Sci 176:67–74. CrossRefGoogle Scholar
  26. 26.
    Andreotti JP, Prazeres PHDM, Magno LAV, Romano-Silva MA, Mintz A, Birbrair A (2018) Neurogenesis in the postnatal cerebellum after injury. Int J Dev Neurosci 67:33–36CrossRefGoogle Scholar
  27. 27.
    Zhou BO, Yue R, Murphy MM, Peyer JG, Morrison SJ (2014) Leptin-receptor-expressing mesenchymal stromal cells represent the main source of bone formed by adult bone marrow. Cell Stem Cell 15(2):154–168. CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Borges I, Sena I, Azevedo P, Andreotti J, Almeida V, Paiva A, Santos G, Guerra D, Prazeres P, Mesquita LL, Silva LSB, Leonel C, Mintz A, Birbrair A (2017) Lung as a niche for hematopoietic progenitors. Stem Cell Rev 13(5):567–574. CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Snippert HJ, Clevers H (2011) Tracking adult stem cells. EMBO Rep 12(2):113–122. CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Spaeth E, Klopp A, Dembinski J, Andreeff M, Marini F (2008) Inflammation and tumor microenvironments: defining the migratory itinerary of mesenchymal stem cells. Gene Ther 15(10):730–738. CrossRefGoogle Scholar
  31. 31.
    Keibel A, Singh V, Sharma MC (2009) Inflammation, microenvironment, and the immune system in cancer progression. Curr Pharm Des 15(17):1949–1955CrossRefGoogle Scholar
  32. 32.
    Andreotti JP, Paiva AE, Prazeres P, Guerra DAP, Silva WN, Vaz RS, Mintz A, Birbrair A (2018) The role of natural killer cells in the uterine microenvironment during pregnancy. Cell Mol Immunol. CrossRefGoogle Scholar
  33. 33.
    Birbrair A, Frenette PS (2016) Niche heterogeneity in the bone marrow. Ann N Y Acad Sci 1370(1):82–96. CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Sena IFG, Borges IT, Lousado L, Azevedo PO, Andreotti JP, Almeida VM, Paiva AE, Santos GSP, Guerra DAP, Prazeres P, Souto L, Mintz A, Birbrair A (2017) LepR+ cells dispute hegemony with Gli1+ cells in bone marrow fibrosis. Cell Cycle 16:1–5. CrossRefGoogle Scholar
  35. 35.
    Azevedo PO, Lousado L, Paiva AE, Andreotti JP, Santos GSP, Sena IFG, Prazeres P, Filev R, Mintz A, Birbrair A (2017) Endothelial cells maintain neural stem cells quiescent in their niche. Neuroscience 363:62–65. CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Paiva AE, Lousado L, Almeida VM, Andreotti JP, Santos GSP, Azevedo PO, Sena IFG, Prazeres PHDM, Borges IT, Azevedo V, Birbrair A (2017) Endothelial cells as precursors for osteoblasts in the metastatic prostate cancer bone. Neoplasia 19:928–931CrossRefGoogle Scholar
  37. 37.
    Lousado L, Prazeres P, Andreotti JP, Paiva AE, Azevedo PO, Santos GSP, Filev R, Mintz A, Birbrair A (2017) Schwann cell precursors as a source for adrenal gland chromaffin cells. Cell Death Dis 8(10):e3072. CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Guerra DAP, Paiva AE, Sena IFG, Azevedo PO, Batista ML Jr, Mintz A, Birbrair A (2017) Adipocytes role in the bone marrow niche. Cytometry A 93:167–171. CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Dias Moura Prazeres PH, Sena IFG, Borges IDT, de Azevedo PO, Andreotti JP, de Paiva AE, de Almeida VM, de Paula Guerra DA, Pinheiro Dos Santos GS, Mintz A, Delbono O, Birbrair A (2017) Pericytes are heterogeneous in their origin within the same tissue. Dev Biol 427(1):6–11. CrossRefGoogle Scholar
  40. 40.
    Prazeres P, Almeida VM, Lousado L, Andreotti JP, Paiva AE, Santos GSP, Azevedo PO, Souto L, Almeida GG, Filev R, Mintz A, Goncalves R, Birbrair A (2017) Macrophages generate pericytes in the developing brain. Cell Mol Neurobiol 38:777–782. CrossRefGoogle Scholar
  41. 41.
    Birbrair A, Sattiraju A, Zhu D, Zulato G, Batista I, Nguyen VT, Messi ML, Solingapuram Sai KK, Marini FC, Delbono O, Mintz A (2017) Novel peripherally derived neural-like stem cells as therapeutic carriers for treating glioblastomas. Stem Cells Transl Med 6(2):471–481. CrossRefGoogle Scholar
  42. 42.
    Birbrair A, Wang ZM, Messi ML, Enikolopov GN, Delbono O (2011) Nestin-GFP transgene reveals neural precursor cells in adult skeletal muscle. PLoS One 6(2):e16816. CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Birbrair A, Zhang T, Files DC, Mannava S, Smith T, Wang ZM, Messi ML, Mintz A, Delbono O (2014) Type-1 pericytes accumulate after tissue injury and produce collagen in an organ-dependent manner. Stem Cell Res Ther 5(6):122. CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Birbrair A, Zhang T, Wang ZM, Messi ML, Enikolopov GN, Mintz A, Delbono O (2013) Skeletal muscle pericyte subtypes differ in their differentiation potential. Stem Cell Res 10(1):67–84. CrossRefGoogle Scholar
  45. 45.
    Birbrair A, Zhang T, Wang ZM, Messi ML, Enikolopov GN, Mintz A, Delbono O (2013) Role of pericytes in skeletal muscle regeneration and fat accumulation. Stem Cells Dev 22(16):2298–2314. CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Birbrair A, Zhang T, Wang ZM, Messi ML, Enikolopov GN, Mintz A, Delbono O (2013) Skeletal muscle neural progenitor cells exhibit properties of NG2-glia. Exp Cell Res 319(1):45–63. CrossRefGoogle Scholar
  47. 47.
    Birbrair A, Zhang T, Wang ZM, Messi ML, Mintz A, Delbono O (2013) Type-1 pericytes participate in fibrous tissue deposition in aged skeletal muscle. Am J Physiol Cell Physiol 305(11):C1098–C1113. CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Birbrair A, Zhang T, Wang ZM, Messi ML, Mintz A, Delbono O (2014) Pericytes: multitasking cells in the regeneration of injured, diseased, and aged skeletal muscle. Front Aging Neurosci 6:245. CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Birbrair A, Zhang T, Wang ZM, Messi ML, Mintz A, Delbono O (2015) Pericytes at the intersection between tissue regeneration and pathology. Clin Sci 128(2):81–93. CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Birbrair A, Zhang T, Wang ZM, Messi ML, Olson JD, Mintz A, Delbono O (2014) Type-2 pericytes participate in normal and tumoral angiogenesis. Am J Physiol Cell Physiol 307(1):C25–C38. CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Birbrair A, Delbono O (2015) Pericytes are essential for skeletal muscle formation. Stem Cell Rev 11(4):547–548. CrossRefGoogle Scholar
  52. 52.
    Prazeres PHDM, Turquetti AOM, Azevedo PO, Barreto RSN, Miglino MA, Mintz A, Delbono O, Birbrair A (2018) Perivascular cell αv integrins as a target to treat skeletal muscle fibrosis. Int J Biochem Cell Biol 99:109–113CrossRefGoogle Scholar
  53. 53.
    Paiva AE, Lousado L, Guerra DAP, Azevedo PO, Sena IFG, Andreotti JP, Santos GSP, Goncalves R, Mintz A, Birbrair A (2018) Pericytes in the premetastatic niche. Cancer Res 78:2779–2786. CrossRefGoogle Scholar
  54. 54.
    Silva WN, Leonel C, Prazeres PHDM, Sena IFG, Guerra DAP, Diniz IMA, Fortuna V, Mintz A, Birbrair A (2018) Role of Schwann cells in cutaneous wound healing. Wound repair and regeneration: official publication of the Wound Healing Society [and] the European Tissue Repair SocietyGoogle Scholar
  55. 55.
    Silva WN, Prazeres P, Paiva AE, Lousado L, Turquetti AOM, Barreto RSN, de Alvarenga EC, Miglino MA, Goncalves R, Mintz A, Birbrair A (2018) Macrophage-derived GPNMB accelerates skin healing. Exp Dermatol 27:630–635. CrossRefGoogle Scholar
  56. 56.
    Costa MA, Paiva AE, Andreotti JP, Cardoso MV, Cardoso CD, Mintz A, Birbrair A (2018) Pericytes constrict blood vessels after myocardial ischemia. J Mol Cell Cardiol 116:1–4. CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Coatti GC, Frangini M, Valadares MC, Gomes JP, Lima NO, Cavacana N, Assoni AF, Pelatti MV, Birbrair A, de Lima ACP, Singer JM, Rocha FMM, Da Silva GL, Mantovani MS, Macedo-Souza LI, Ferrari MFR, Zatz M (2017) Pericytes extend survival of ALS SOD1 mice and induce the expression of antioxidant enzymes in the murine model and in IPSCs derived neuronal cells from an ALS patient. Stem Cell Rev 13:686–698. CrossRefGoogle Scholar
  58. 58.
    Sena IFG, Prazeres P, Santos GSP, Borges IT, Azevedo PO, Andreotti JP, Almeida VM, Paiva AE, Guerra DAP, Lousado L, Souto L, Mintz A, Birbrair A (2017) Identity of Gli1+ cells in the bone marrow. Exp Hematol 54:12–16. CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Hanoun M, Maryanovich M, Arnal-Estape A, Frenette PS (2015) Neural regulation of hematopoiesis, inflammation, and cancer. Neuron 86(2):360–373. CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Arranz L, Sanchez-Aguilera A, Martin-Perez D, Isern J, Langa X, Tzankov A, Lundberg P, Muntion S, Tzeng YS, Lai DM, Schwaller J, Skoda RC, Mendez-Ferrer S (2014) Neuropathy of haematopoietic stem cell niche is essential for myeloproliferative neoplasms. Nature 512(7512):78–81. CrossRefGoogle Scholar
  61. 61.
    Hanoun M, Zhang D, Mizoguchi T, Pinho S, Pierce H, Kunisaki Y, Lacombe J, Armstrong SA, Duhrsen U, Frenette PS (2014) Acute myelogenous leukemia-induced sympathetic neuropathy promotes malignancy in an altered hematopoietic stem cell niche. Cell Stem Cell 15(3):365–375. CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Salomoni P, Betts-Henderson J (2011) The role of PML in the nervous system. Mol Neurobiol 43(2):114–123. CrossRefGoogle Scholar
  63. 63.
    Florean C, Schnekenburger M, Grandjenette C, Dicato M, Diederich M (2011) Epigenomics of leukemia: from mechanisms to therapeutic applications. Epigenomics 3(5):581–609. CrossRefGoogle Scholar
  64. 64.
    Lengfelder E, Hofmann WK, Nowak D (2012) Impact of arsenic trioxide in the treatment of acute promyelocytic leukemia. Leukemia 26(3):433–442. CrossRefGoogle Scholar
  65. 65.
    Hu J, Liu YF, Wu CF, Xu F, Shen ZX, Zhu YM, Li JM, Tang W, Zhao WL, Wu W, Sun HP, Chen QS, Chen B, Zhou GB, Zelent A, Waxman S, Wang ZY, Chen SJ, Chen Z (2009) Long-term efficacy and safety of all-trans retinoic acid/arsenic trioxide-based therapy in newly diagnosed acute promyelocytic leukemia. Proc Natl Acad Sci U S A 106(9):3342–3347. CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    George B, Mathews V, Poonkuzhali B, Shaji RV, Srivastava A, Chandy M (2004) Treatment of children with newly diagnosed acute promyelocytic leukemia with arsenic trioxide: a single center experience. Leukemia 18(10):1587–1590. CrossRefGoogle Scholar
  67. 67.
    Kumazaki M, Ando H, Sasaki A, Koshimizu TA, Ushijima K, Hosohata K, Oshima Y, Fujimura A (2011) Protective effect of alpha-lipoic acid against arsenic trioxide-induced acute cardiac toxicity in rats. J Pharmacol Sci 115(2):244–248CrossRefGoogle Scholar
  68. 68.
    Wang M, Sun G, Wu P, Chen R, Yao F, Qin M, Luo Y, Sun H, Zhang Q, Dong X, Sun X (2013) Salvianolic acid B prevents arsenic trioxide-induced cardiotoxicity in vivo and enhances its anticancer activity in vitro. Evid Based Complement Alternat Med 2013:759483–759489. CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Ame-Thomas P, Maby-El Hajjami H, Monvoisin C, Jean R, Monnier D, Caulet-Maugendre S, Guillaudeux T, Lamy T, Fest T, Tarte K (2007) Human mesenchymal stem cells isolated from bone marrow and lymphoid organs support tumor B-cell growth: role of stromal cells in follicular lymphoma pathogenesis. Blood 109(2):693–702. CrossRefGoogle Scholar
  70. 70.
    Karnoub AE, Dash AB, Vo AP, Sullivan A, Brooks MW, Bell GW, Richardson AL, Polyak K, Tubo R, Weinberg RA (2007) Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature 449(7162):557–563. CrossRefGoogle Scholar
  71. 71.
    Prantl L, Muehlberg F, Navone NM, Song YH, Vykoukal J, Logothetis CJ, Alt EU (2010) Adipose tissue-derived stem cells promote prostate tumor growth. Prostate 70(15):1709–1715. CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Kansy BA, Dissmann PA, Hemeda H, Bruderek K, Westerkamp AM, Jagalski V, Schuler P, Kansy K, Lang S, Dumitru CA, Brandau S (2014) The bidirectional tumor--mesenchymal stromal cell interaction promotes the progression of head and neck cancer. Stem Cell Res Ther 5(4):95. CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Zhu W, Xu W, Jiang R, Qian H, Chen M, Hu J, Cao W, Han C, Chen Y (2006) Mesenchymal stem cells derived from bone marrow favor tumor cell growth in vivo. Exp Mol Pathol 80(3):267–274. CrossRefGoogle Scholar
  74. 74.
    Li W, Zhou Y, Yang J, Zhang X, Zhang H, Zhang T, Zhao S, Zheng P, Huo J, Wu H (2015) Gastric cancer-derived mesenchymal stem cells prompt gastric cancer progression through secretion of interleukin-8. J Exp Clin Cancer Res 34:52. CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Hossain A, Gumin J, Gao F, Figueroa J, Shinojima N, Takezaki T, Priebe W, Villarreal D, Kang SG, Joyce C, Sulman E, Wang Q, Marini FC, Andreeff M, Colman H, Lang FF (2015) Mesenchymal stem cells isolated from human gliomas increase proliferation and maintain stemness of glioma stem cells through the IL-6/gp130/STAT3 pathway. Stem Cells 33(8):2400–2415. CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Guerra DAP, Paiva AE, Sena IFG, Azevedo PO, Silva WN, Mintz A, Birbrair A (2018) Targeting glioblastoma-derived pericytes improves chemotherapeutic outcome. Angiogenesis. CrossRefGoogle Scholar
  77. 77.
    Nabha SM, dos Santos EB, Yamamoto HA, Belizi A, Dong Z, Meng H, Saliganan A, Sabbota A, Bonfil RD, Cher ML (2008) Bone marrow stromal cells enhance prostate cancer cell invasion through type I collagen in an MMP-12 dependent manner. Int J Cancer 122(11):2482–2490. CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Natural SciencesFederal University of São João del ReiSão João Del ReyBrazil
  2. 2.Department of PathologyFederal University of Minas GeraisBelo HorizonteBrazil
  3. 3.Department of BiochemistryFederal University of São PauloSão PauloBrazil
  4. 4.Faculty of Pharmaceutical Sciences, Food and NutritionFederal University of Mato Grosso do SulCampo GrandeBrazil
  5. 5.Department of RadiologyColumbia University Medical CenterNew YorkUSA

Personalised recommendations