Cytokine & Growth Factor Reviews
Volume 21, Issue 1 , Pages 49-59 , February 2010

Transforming growth factor beta (TGF-β) and inflammation in cancer

  • Brian Bierie

      Affiliations

    • Department of Cancer Biology, Vanderbilt University, Nashville, TN, USA
    • ,
  • Harold L. Moses

      Affiliations

    • Department of Cancer Biology, Vanderbilt University, Nashville, TN, USA
    • Department of Medicine, Vanderbilt University, Nashville, TN, USA
    • Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA
    • Corresponding Author InformationCorresponding author at: 698 Preston Research Building, 2220 Pierce Avenue, Nashville, TN 37232-6838, USA. Tel.: +1 615 936 1782; fax: +1 615 936 1790.

References 

  1. Kehrl JH, Wakefield LM, Roberts AB, Jakowlew S, Alvarez-Mon M, Derynck R, et al. Production of transforming growth factor beta by human T lymphocytes and its potential role in the regulation of T cell growth. J Exp Med. 1986;163(5):1037–1050
  2. Kehrl JH, Roberts AB, Wakefield LM, Jakowlew S, Sporn MB, Fauci AS. Transforming growth factor beta is an important immunomodulatory protein for human B lymphocytes. J Immunol. 1986;137(12):3855–3860
  3. Rook AH, Kehrl JH, Wakefield LM, Roberts AB, Sporn MB, Burlington DB, et al. Effects of transforming growth factor beta on the functions of natural killer cells: depressed cytolytic activity and blunting of interferon responsiveness. J Immunol. 1986;136(10):3916–3920
  4. Fontana A, Bodmer S, Frei K, Malipiero U, Siepl C. Expression of TGF-beta 2 in human glioblastoma: a role in resistance to immune rejection?. Ciba Found Symp. 1991;157:232–238discussion 238-41
  5. Mule JJ, Schwarz SL, Roberts AB, Sporn MB, Rosenberg SA. Transforming growth factor-beta inhibits the in vitro generation of lymphokine-activated killer cells and cytotoxic T cells. Cancer Immunol Immunother. 1988;26(2):95–100
  6. Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002;420(6917):860–867
  7. de Visser KE, Eichten A, Coussens LM. Paradoxical roles of the immune system during cancer development. Nat Rev Cancer. 2006;6(1):24–37
  8. Li MO, Wan YY, Sanjabi S, Robertson AK, Flavell RA. Transforming growth factor-beta regulation of immune responses. Annu Rev Immunol. 2006;24:99–146
  9. Wrzesinski SH, Wan YY, Flavell RA. Transforming growth factor-beta and the immune response: implications for anticancer therapy. Clin Cancer Res. 2007;13(18 Pt 1):5262–5270
  10. Chen JJ, Sun Y, Nabel GJ. Regulation of the proinflammatory effects of Fas ligand (CD95L). Science. 1998;282(5394):1714–1717
  11. Bierie B, Moses HL. Tumour microenvironment: TGFbeta: the molecular Jekyll and Hyde of cancer. Nat Rev Cancer. 2006;6(7):506–520
  12. Massague J. TGFbeta in Cancer. Cell. 2008;134(2):215–230
  13. Derynck R, Goeddel DV, Ullrich A, Gutterman JU, Williams RD, Bringman TS, et al. Synthesis of messenger RNAs for transforming growth factors alpha and beta and the epidermal growth factor receptor by human tumors. Cancer Res. 1987;47(3):707–712
  14. Dickson RB, Kasid A, Huff KK, Bates SE, Knabbe C, Bronzert D, et al. Activation of growth factor secretion in tumorigenic states of breast cancer induced by 17 beta-estradiol or v-Ha-ras oncogene. Proc Natl Acad Sci USA. 1987;84(3):837–841
  15. Wojtowicz-Praga S. Reversal of tumor-induced immunosuppression by TGF-beta inhibitors. Invest New Drugs. 2003;21(1):21–32
  16. Levy L, Hill CS. Alterations in components of the TGF-beta superfamily signaling pathways in human cancer. Cytokine Growth Factor Rev. 2006;17(1–2):41–58
  17. Stover DG, Bierie B, Moses HL. A delicate balance: TGF-beta and the tumor microenvironment. J Cell Biochem. 2007;
  18. Abe M, Oda N, Sato Y. Cell-associated activation of latent transforming growth factor-beta by calpain. J Cell Physiol. 1998;174(2):186–193
  19. Munger JS, Huang X, Kawakatsu H, Griffiths MJ, Dalton SL, Wu J, et al. The integrin alpha v beta 6 binds and activates latent TGF beta 1: a mechanism for regulating pulmonary inflammation and fibrosis. Cell. 1999;96(3):319–328
  20. Lyons RM, Keski-Oja J, Moses HL. Proteolytic activation of latent transforming growth factor-beta from fibroblast-conditioned medium. J Cell Biol. 1988;106(5):1659–1665
  21. Akita K, Okuno M, Enya M, Imai S, Moriwaki H, Kawada N, et al. Impaired liver regeneration in mice by lipopolysaccharide via TNF-alpha/kallikrein-mediated activation of latent TGF-beta. Gastroenterology. 2002;123(1):352–364
  22. Taipale J, Lohi J, Saarinen J, Kovanen PT, Keski-Oja J. Human mast cell chymase and leukocyte elastase release latent transforming growth factor-beta 1 from the extracellular matrix of cultured human epithelial and endothelial cells. J Biol Chem. 1995;270(9):4689–4696
  23. Miyazono K, Heldin CH. Role for carbohydrate structures in TGF-beta 1 latency. Nature. 1989;338(6211):158–160
  24. Yu Q, Stamenkovic I. Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis. Genes Dev. 2000;14(2):163–176
  25. Schultz-Cherry S, Hinshaw VS. Influenza virus neuraminidase activates latent transforming growth factor beta. J Virol. 1996;70(12):8624–8629
  26. Schultz-Cherry S, Murphy-Ullrich JE. Thrombospondin causes activation of latent transforming growth factor-beta secreted by endothelial cells by a novel mechanism. J Cell Biol. 1993;122(4):923–932
  27. Barcellos-Hoff MH, Dix TA. Redox-mediated activation of latent transforming growth factor-beta 1. Mol Endocrinol. 1996;10(9):1077–1083
  28. Shi Y, Massague J. Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell. 2003;113(6):685–700
  29. Derynck R, Zhang YE. Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature. 2003;425(6958):577–584
  30. Lee MK, Pardoux C, Hall MC, Lee PS, Warburton D, Qing J, et al. TGF-beta activates Erk MAP kinase signalling through direct phosphorylation of ShcA. EMBO J. 2007;26(17):3957–3967
  31. Feng XH, Derynck R. Specificity and versatility in TGF-signaling through Smads. Annu Rev Cell Dev Biol. 2005;
  32. Daly AC, Randall RA, Hill CS. Transforming growth factor beta-induced Smad1/5 phosphorylation in epithelial cells is mediated by novel receptor complexes and is essential for anchorage-independent growth. Mol Cell Biol. 2008;28(22):6889–6902
  33. Moustakas A, Heldin CH. Signaling networks guiding epithelial-mesenchymal transitions during embryogenesis and cancer progression. Cancer Sci. 2007;98(10):1512–1520
  34. Yamashita M, Fatyol K, Jin C, Wang X, Liu Z, Zhang YE. TRAF6 mediates Smad-independent activation of JNK and p38 by TGF-beta. Mol Cell. 2008;31(6):918–924
  35. Bierie B, Moses HL. TGF-beta and cancer. Cytokine Growth Factor Rev. 2006;17(1–2):29–40
  36. Zeng Q, Phukan S, Xu Y, Sadim M, Rosman DS, Pennison M, et al. Tgfbr1 haploinsufficiency is a potent modifier of colorectal cancer development. Cancer Res. 2009;69(2):678–686
  37. Valle L, Serena-Acedo T, Liyanarachchi S, Hampel H, Comeras I, Li Z, et al. Germline allele-specific expression of TGFBR1 confers an increased risk of colorectal cancer. Science. 2008;321(5894):1361–1365
  38. Grady WM, Markowitz SD. Genetic and epigenetic alterations in colon cancer. Annu Rev Genomics Hum Genet. 2002;3:101–128
  39. Kim BG, Li C, Qiao W, Mamura M, Kasprzak B, Anver M, et al. Smad4 signalling in T cells is required for suppression of gastrointestinal cancer. Nature. 2006;441(7096):1015–1019
  40. Shipitsin M, Campbell LL, Argani P, Weremowicz S, Bloushtain-Qimron N, Yao J, et al. Molecular definition of breast tumor heterogeneity. Cancer Cell. 2007;11(3):259–273
  41. Kang SH, Bang YJ, Im YH, Yang HK, Lee DA, Lee HY, et al. Transcriptional repression of the transforming growth factor-beta type I receptor gene by DNA methylation results in the development of TGF-beta resistance in human gastric cancer. Oncogene. 1999;18(51):7280–7286
  42. Kim SJ, Im YH, Markowitz SD, Bang YJ. Molecular mechanisms of inactivation of TGF-beta receptors during carcinogenesis. Cytokine Growth Factor Rev. 2000;11(1–2):159–168
  43. Rojas A, Meherem S, Kim YH, Washington MK, Willis JE, Markowitz SD, et al. The aberrant methylation of TSP1 suppresses TGF-beta1 activation in colorectal cancer. Int J Cancer. 2008;123(1):14–21
  44. Aitchison AA, Veerakumarasivam A, Vias M, Kumar R, Hamdy FC, Neal DE, et al. Promoter methylation correlates with reduced Smad4 expression in advanced prostate cancer. Prostate. 2008;68(6):661–674
  45. Hinshelwood RA, Huschtscha LI, Melki J, Stirzaker C, Abdipranoto A, Vissel B, et al. Concordant epigenetic silencing of transforming growth factor-beta signaling pathway genes occurs early in breast carcinogenesis. Cancer Res. 2007;67(24):11517–11527
  46. Nakao A, Afrakhte M, Moren A, Nakayama T, Christian JL, Heuchel R, et al. Identification of Smad7, a TGFbeta-inducible antagonist of TGF-beta signalling. Nature. 1997;389(6651):631–635
  47. Hayashi H, Abdollah S, Qiu Y, Cai J, Xu YY, Grinnell BW, et al. The MAD-related protein Smad7 associates with the TGFbeta receptor and functions as an antagonist of TGFbeta signaling. Cell. 1997;89(7):1165–1173
  48. Kavsak P, Rasmussen RK, Causing CG, Bonni S, Zhu H, Thomsen GH, et al. Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGF beta receptor for degradation. Mol Cell. 2000;6(6):1365–1375
  49. Ebisawa T, Fukuchi M, Murakami G, Chiba T, Tanaka K, Imamura T, et al. Smurf1 interacts with transforming growth factor-beta type I receptor through Smad7 and induces receptor degradation. J Biol Chem. 2001;276(16):12477–12480
  50. Inoue Y, Imamura T. Regulation of TGF-beta family signaling by E3 ubiquitin ligases. Cancer Sci. 2008;99(11):2107–2112
  51. Shi W, Sun C, He B, Xiong W, Shi X, Yao D, et al. GADD34-PP1c recruited by Smad7 dephosphorylates TGFbeta type I receptor. J Cell Biol. 2004;164(2):291–300
  52. Datta PK, Moses HL. STRAP and Smad7 synergize in the inhibition of transforming growth factor beta signaling. Mol Cell Biol. 2000;20(9):3157–3167
  53. Ferrigno O, Lallemand F, Verrecchia F, L’Hoste S, Camonis J, Atfi A, et al. Yes-associated protein (YAP65) interacts with Smad7 and potentiates its inhibitory activity against TGF-beta/Smad signaling. Oncogene. 2002;21(32):4879–4884
  54. Stroschein SL, Wang W, Zhou S, Zhou Q, Luo K. Negative feedback regulation of TGF-beta signaling by the SnoN oncoprotein. Science. 1999;286(5440):771–774
  55. Luo K, Stroschein SL, Wang W, Chen D, Martens E, Zhou S, et al. The Ski oncoprotein interacts with the Smad proteins to repress TGFbeta signaling. Genes Dev. 1999;13(17):2196–2206
  56. Siegel PM, Massague J. Cytostatic and apoptotic actions of TGF-beta in homeostasis and cancer. Nat Rev Cancer. 2003;3(11):807–821
  57. Heldin CH, Landstrom M, Moustakas A. Mechanism of TGF-beta signaling to growth arrest, apoptosis, and epithelial-mesenchymal transition. Curr Opin Cell Biol. 2009;21(2):166–176
  58. Daniel CW, Robinson SD. Regulation of mammary growth and function by TGF-beta. Mol Reprod Dev. 1992;32(2):145–151
  59. Daniel CW, Silberstein GB, Van Horn K, Strickland P, Robinson S. TGF-beta 1-induced inhibition of mouse mammary ductal growth: developmental specificity and characterization. Dev Biol. 1989;135(1):20–30
  60. Silberstein GB, Daniel CW. Reversible inhibition of mammary gland growth by transforming growth factor-beta. Science. 1987;237(4812):291–293
  61. Pierce DF, Johnson MD, Matsui Y, Robinson SD, Gold LI, Purchio AF, et al. Inhibition of mammary duct development but not alveolar outgrowth during pregnancy in transgenic mice expressing active TGF-beta 1. Genes Dev. 1993;7(12A):2308–2317
  62. Boulanger CA, Wagner KU, Smith GH. Parity-induced mouse mammary epithelial cells are pluripotent, self-renewing and sensitive to TGF-beta1 expression. Oncogene. 2005;24(4):552–560
  63. Jhappan C, Geiser AG, Kordon EC, Bagheri D, Hennighausen L, Roberts AB, et al. Targeting expression of a transforming growth factor beta 1 transgene to the pregnant mammary gland inhibits alveolar development and lactation. EMBO J. 1993;12(5):1835–1845
  64. Kordon EC, McKnight RA, Jhappan C, Hennighausen L, Merlino G, Smith GH. Ectopic TGF beta 1 expression in the secretory mammary epithelium induces early senescence of the epithelial stem cell population. Dev Biol. 1995;168(1):47–61
  65. Ewan KB, Shyamala G, Ravani SA, Tang Y, Akhurst R, Wakefield L, et al. Latent transforming growth factor-beta activation in mammary gland: regulation by ovarian hormones affects ductal and alveolar proliferation. Am J Pathol. 2002;160(6):2081–2093
  66. Gorska AE, Jensen RA, Shyr Y, Aakre ME, Bhowmick NA, Moses HL. Transgenic mice expressing a dominant-negative mutant type II transforming growth factor-beta receptor exhibit impaired mammary development and enhanced mammary tumor formation. Am J Pathol. 2003;163(4):1539–1549
  67. Lenferink AE, Magoon J, Pepin MC, Guimond A, O’Connor-McCourt MD. Expression of TGF-beta type II receptor antisense RNA impairs TGF-beta signaling in vitro and promotes mammary gland differentiation in vivo. Int J Cancer. 2003;107(6):919–928
  68. Pierce DF, Gorska AE, Chytil A, Meise KS, Page DL, Coffey RJ, et al. Mammary tumor suppression by transforming growth factor beta 1 transgene expression. Proc Natl Acad Sci USA. 1995;92(10):4254–4258
  69. Boulanger CA, Smith GH. Reducing mammary cancer risk through premature stem cell senescence. Oncogene. 2001;20(18):2264–2272
  70. Siegel PM, Shu W, Cardiff RD, Muller WJ, Massague J. Transforming growth factor beta signaling impairs Neu-induced mammary tumorigenesis while promoting pulmonary metastasis. Proc Natl Acad Sci USA. 2003;100(14):8430–8435
  71. Muraoka-Cook RS, Kurokawa H, Koh Y, Forbes JT, Roebuck LR, Barcellos-Hoff MH, et al. Conditional overexpression of active transforming growth factor beta1 in vivo accelerates metastases of transgenic mammary tumors. Cancer Res. 2004;64(24):9002–9011
  72. Muraoka-Cook RS, Shin I, Yi JY, Easterly E, Barcellos-Hoff MH, Yingling JM, et al. Activated type I TGFbeta receptor kinase enhances the survival of mammary epithelial cells and accelerates tumor progression. Oncogene. 2006;25(24):3408–3423
  73. Yang YA, Dukhanina O, Tang B, Mamura M, Letterio JJ, MacGregor J, et al. Lifetime exposure to a soluble TGF-beta antagonist protects mice against metastasis without adverse side effects. J Clin Invest. 2002;109(12):1607–1615
  74. Forrester E, Chytil A, Bierie B, Aakre M, Gorska AE, Sharif-Afshar AR, et al. Effect of conditional knockout of the type II TGF-beta receptor gene in mammary epithelia on mammary gland development and polyomavirus middle T antigen induced tumor formation and metastasis. Cancer Res. 2005;65(6):2296–2302
  75. Bierie B, Stover DG, Abel TW, Chytil A, Gorska AE, Aakre M, et al. Transforming growth factor-beta regulates mammary carcinoma cell survival and interaction with the adjacent microenvironment. Cancer Res. 2008;68(6):1809–1819
  76. Yang L, Huang J, Ren X, Gorska AE, Chytil A, Aakre M, et al. Abrogation of TGF beta signaling in mammary carcinomas recruits Gr-1+ CD11b+ myeloid cells that promote metastasis. Cancer Cell. 2008;13(1):23–35
  77. Bierie B, Chung CH, Parker JS, Stover DG, Cheng N, Chytil A, et al. Abrogation of TGF-beta signaling enhances chemokine production and correlates with prognosis in human breast cancer. J Clin Invest. 2009;119(6):1571–1582
  78. Padua D, Zhang XH, Wang Q, Nadal C, Gerald WL, Gomis RR, et al. TGFbeta primes breast tumors for lung metastasis seeding through angiopoietin-like 4. Cell. 2008;133(1):66–77
  79. Marigo I, Dolcetti L, Serafini P, Zanovello P, Bronte V. Tumor-induced tolerance and immune suppression by myeloid derived suppressor cells. Immunol Rev. 2008;222:162–179
  80. Gallina G, Dolcetti L, Serafini P, De Santo C, Marigo I, Colombo MP, et al. Tumors induce a subset of inflammatory monocytes with immunosuppressive activity on CD8+ T cells. J Clin Invest. 2006;116(10):2777–2790
  81. Sinha P, Clements VK, Bunt SK, Albelda SM, Ostrand-Rosenberg S. Cross-talk between myeloid-derived suppressor cells and macrophages subverts tumor immunity toward a type 2 response. J Immunol. 2007;179(2):977–983
  82. Sica A, Bronte V. Altered macrophage differentiation and immune dysfunction in tumor development. J Clin Invest. 2007;117(5):1155–1166
  83. Kitamura T, Kometani K, Hashida H, Matsunaga A, Miyoshi H, Hosogi H, et al. SMAD4-deficient intestinal tumors recruit CCR1+ myeloid cells that promote invasion. Nat Genet. 2007;39(4):467–475
  84. Almand B, Clark JI, Nikitina E, van Beynen J, English NR, Knight SC, et al. Increased production of immature myeloid cells in cancer patients: a mechanism of immunosuppression in cancer. J Immunol. 2001;166(1):678–689
  85. Serafini P, Meckel K, Kelso M, Noonan K, Califano J, Koch W, et al. Phosphodiesterase-5 inhibition augments endogenous antitumor immunity by reducing myeloid-derived suppressor cell function. J Exp Med. 2006;203(12):2691–2702
  86. Filipazzi P, Valenti R, Huber V, Pilla L, Canese P, Iero M, et al. Identification of a new subset of myeloid suppressor cells in peripheral blood of melanoma patients with modulation by a granulocyte-macrophage colony-stimulation factor-based antitumor vaccine. J Clin Oncol. 2007;25(18):2546–2553
  87. Zea AH, Rodriguez PC, Atkins MB, Hernandez C, Signoretti S, Zabaleta J, et al. Arginase-producing myeloid suppressor cells in renal cell carcinoma patients: a mechanism of tumor evasion. Cancer Res. 2005;65(8):3044–3048
  88. Kulkarni AB, Huh CG, Becker D, Geiser A, Lyght M, Flanders KC, et al. Transforming growth factor beta 1 null mutation in mice causes excessive inflammatory response and early death. Proc Natl Acad Sci USA. 1993;90(2):770–774
  89. Shull MM, Ormsby I, Kier AB, Pawlowski S, Diebold RJ, Yin M, et al. Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease. Nature. 1992;359(6397):693–699
  90. Gorelik L, Flavell RA. Abrogation of TGFbeta signaling in T cells leads to spontaneous T cell differentiation and autoimmune disease. Immunity. 2000;12(2):171–181
  91. McKarns SC, Schwartz RH, Kaminski NE. Smad3 is essential for TGF-beta 1 to suppress IL-2 production and TCR-induced proliferation, but not IL-2-induced proliferation. J Immunol. 2004;172(7):4275–4284
  92. Ruegemer JJ, Ho SN, Augustine JA, Schlager JW, Bell MP, McKean DJ, et al. Regulatory effects of transforming growth factor-beta on IL-2- and IL-4-dependent T cell-cycle progression. J Immunol. 1990;144(5):1767–1776
  93. Wolfraim LA, Walz TM, James Z, Fernandez T, Letterio JJ. p21Cip1 and p27Kip1 act in synergy to alter the sensitivity of naive T cells to TGF-beta-mediated G1 arrest through modulation of IL-2 responsiveness. J Immunol. 2004;173(5):3093–3102
  94. Gorelik L, Flavell RA. Transforming growth factor-beta in T-cell biology. Nat Rev Immunol. 2002;2(1):46–53
  95. Gorelik L, Flavell RA. Immune-mediated eradication of tumors through the blockade of transforming growth factor-beta signaling in T cells. Nat Med. 2001;7(10):1118–1122
  96. Alleva DG, Walker TM, Elgert KD. Induction of macrophage suppressor activity by fibrosarcoma-derived transforming growth factor-beta 1: contrasting effects on resting and activated macrophages. J Leukoc Biol. 1995;57(6):919–928
  97. Chen ML, Pittet MJ, Gorelik L, Flavell RA, Weissleder R, von Boehmer H, et al. Regulatory T cells suppress tumor-specific CD8 T cell cytotoxicity through TGF-beta signals in vivo. Proc Natl Acad Sci USA. 2005;102(2):419–424
  98. Zhang Q, Yang X, Pins M, Javonovic B, Kuzel T, Kim SJ, et al. Adoptive transfer of tumor-reactive transforming growth factor-beta-insensitive CD8+ T cells: eradication of autologous mouse prostate cancer. Cancer Res. 2005;65(5):1761–1769
  99. Park JA, Wang E, Kurt RA, Schluter SF, Hersh EM, Akporiaye ET. Expression of an antisense transforming growth factor-beta1 transgene reduces tumorigenicity of EMT6 mammary tumor cells. Cancer Gene Ther. 1997;4(1):42–50
  100. Mukherjee P, Ginardi AR, Madsen CS, Tinder TL, Jacobs F, Parker J, et al. MUC1-specific CTLs are non-functional within a pancreatic tumor microenvironment. Glycoconj J. 2001;18(11–12):931–942
  101. Ranges GE, Figari IS, Espevik T, Palladino MA. Inhibition of cytotoxic T cell development by transforming growth factor beta and reversal by recombinant tumor necrosis factor alpha. J Exp Med. 1987;166(4):991–998
  102. Ahmadzadeh M, Rosenberg SA. TGF-beta 1 attenuates the acquisition and expression of effector function by tumor antigen-specific human memory CD8 T cells. J Immunol. 2005;174(9):5215–5223
  103. Smyth MJ, Strobl SL, Young HA, Ortaldo JR, Ochoa AC. Regulation of lymphokine-activated killer activity and pore-forming protein gene expression in human peripheral blood CD8+ T lymphocytes. Inhibition by transforming growth factor-beta. J Immunol. 1991;146(10):3289–3297
  104. Thomas DA, Massague J. TGF-beta directly targets cytotoxic T cell functions during tumor evasion of immune surveillance. Cancer Cell. 2005;8(5):369–380
  105. Bonig H, Banning U, Hannen M, Kim YM, Verheyen J, Mauz-Korholz C, et al. Transforming growth factor-beta1 suppresses interleukin-15-mediated interferon-gamma production in human T lymphocytes. Scand J Immunol. 1999;50(6):612–618
  106. Kontani K, Kajino K, Huangi CL, Fujino S, Taguchi O, Yamauchi A, et al. Spontaneous elicitation of potent antitumor immunity and eradication of established tumors by administration of DNA encoding soluble transforming growth factor-beta II receptor without active antigen-sensitization. Cancer Immunol Immunother. 2005;1–9
  107. Arteaga CL, Hurd SD, Winnier AR, Johnson MD, Fendly BM, Forbes JT. Anti-transforming growth factor (TGF)-beta antibodies inhibit breast cancer cell tumorigenicity and increase mouse spleen natural killer cell activity. Implications for a possible role of tumor cell/host TGF-beta interactions in human breast cancer progression. J Clin Invest. 1993;92(6):2569–2576
  108. Arteaga CL, Koli KM, Dugger TC, Clarke R. Reversal of tamoxifen resistance of human breast carcinomas in vivo by neutralizing antibodies to transforming growth factor-beta. J Natl Cancer Inst. 1999;91(1):46–53
  109. Ma D, Niederkorn JY. Transforming growth factor-beta down-regulates major histocompatibility complex class I antigen expression and increases the susceptibility of uveal melanoma cells to natural killer cell-mediated cytolysis. Immunology. 1995;86(2):263–269
  110. Lee YJ, Han Y, Lu HT, Nguyen V, Qin H, Howe PH, et al. TGF-beta suppresses IFN-gamma induction of class II MHC gene expression by inhibiting class II transactivator messenger RNA expression. J Immunol. 1997;158(5):2065–2075
  111. Geiser AG, Letterio JJ, Kulkarni AB, Karlsson S, Roberts AB, Sporn MB. Transforming growth factor beta 1 (TGF-beta 1) controls expression of major histocompatibility genes in the postnatal mouse: aberrant histocompatibility antigen expression in the pathogenesis of the TGF-beta 1 null mouse phenotype. Proc Natl Acad Sci USA. 1993;90(21):9944–9948
  112. Johns LD, Babcock G, Green D, Freedman M, Sriram S, Ransohoff RM. Transforming growth factor-beta 1 differentially regulates proliferation and MHC class-II antigen expression in forebrain and brainstem astrocyte primary cultures. Brain Res. 1992;585(1–2):229–236
  113. Ghiringhelli F, Menard C, Terme M, Flament C, Taieb J, Chaput N, et al. CD4+CD25+ regulatory T cells inhibit natural killer cell functions in a transforming growth factor-beta-dependent manner. J Exp Med. 2005;202(8):1075–1085
  114. Smyth MJ, Teng MW, Swann J, Kyparissoudis K, Godfrey DI, Hayakawa Y. CD4+CD25+ T Regulatory Cells Suppress NK Cell-Mediated Immunotherapy of Cancer. J Immunol. 2006;176(3):1582–1587
  115. Castriconi R, Cantoni C, Della Chiesa M, Vitale M, Marcenaro E, Conte R, et al. Transforming growth factor beta 1 inhibits expression of NKp30 and NKG2D receptors: consequences for the NK-mediated killing of dendritic cells. Proc Natl Acad Sci USA. 2003;100(7):4120–4125
  116. Lee JC, Lee KM, Kim DW, Heo DS. Elevated TGF-beta1 secretion and down-modulation of NKG2D underlies impaired NK cytotoxicity in cancer patients. J Immunol. 2004;172(12):7335–7340
  117. Reibman J, Meixler S, Lee TC, Gold LI, Cronstein BN, Haines KA, et al. Transforming growth factor beta 1, a potent chemoattractant for human neutrophils, bypasses classic signal-transduction pathways. Proc Natl Acad Sci USA. 1991;88(15):6805–6809
  118. Hahne M, Rimoldi D, Schroter M, Romero P, Schreier M, French LE, et al. Melanoma cell expression of Fas(Apo-1/CD95) ligand: implications for tumor immune escape. Science. 1996;274(5291):1363–1366
  119. Bombara C, Ignotz RA. TGF-beta inhibits proliferation of and promotes differentiation of human promonocytic leukemia cells. J Cell Physiol. 1992;153(1):30–37
  120. Fontana A, Constam DB, Frei K, Malipiero U, Pfister HW. Modulation of the immune response by transforming growth factor beta. Int Arch Allergy Immunol. 1992;99(1):1–7
  121. Haak-Frendscho M, Wynn TA, Czuprynski CJ, Paulnock D. Transforming growth factor-beta 1 inhibits activation of macrophage cell line RAW 264.7 for cell killing. Clin Exp Immunol. 1990;82(2):404–410
  122. McDonald PP, Fadok VA, Bratton D, Henson PM. Transcriptional and translational regulation of inflammatory mediator production by endogenous TGF-beta in macrophages that have ingested apoptotic cells. J Immunol. 1999;163(11):6164–6172
  123. Fadok VA, Bratton DL, Konowal A, Freed PW, Westcott JY, Henson PM. Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF. J Clin Invest. 1998;101(4):890–898
  124. Bogdan C, Nathan C. Modulation of macrophage function by transforming growth factor beta, interleukin-4, and interleukin-10. Ann N Y Acad Sci. 1993;685:713–739
  125. Feinberg MW, Shimizu K, Lebedeva M, Haspel R, Takayama K, Chen Z, et al. Essential role for Smad3 in regulating MCP-1 expression and vascular inflammation. Circ Res. 2004;94(5):601–608
  126. Wang J, Guan E, Roderiquez G, Calvert V, Alvarez R, Norcross MA. Role of tyrosine phosphorylation in ligand-independent sequestration of CXCR4 in human primary monocytes-macrophages. J Biol Chem. 2001;276(52):49236–49243
  127. Orimo A, Gupta PB, Sgroi DC, Arenzana-Seisdedos F, Delaunay T, Naeem R, et al. Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 Secretion. Cell. 2005;121(3):335–348
  128. Gruber BL, Marchese MJ, Kew RR. Transforming growth factor-beta 1 mediates mast cell chemotaxis. J Immunol. 1994;152(12):5860–5867
  129. Maghazachi AA, al-Aoukaty A. Transforming growth factor-beta 1 is chemotactic for interleukin-2-activated natural killer cells. Nat Immun. 1993;12(2):57–65

PII: S1359-6101(09)00115-4

doi: 10.1016/j.cytogfr.2009.11.008

Cytokine & Growth Factor Reviews
Volume 21, Issue 1 , Pages 49-59 , February 2010

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