Transforming Growth Factor-Beta: Possible Roles in Carcinogenesis

  • K. C. Flanders
  • M. B. Sporn
  • A. B. Roberts
Conference paper


Transforming growth factor “-beta” (TGF-ß) is a multifunctional regulator of cell growth and differentiation which exhibits context dependent biological effects. Thus, in vitro, TGF-ß can stimulate or inhibit proliferation, promote or block differentiation, and modulate cellular function depending on the cell type and cell environment (Roberts et al. 1988a; Sporn and Roberts 1988). Structurally, the active form of TGF-ß is a disulfide crosslinked homodimer with a molecular weight of 25 kDa in the unreduced form, with each monomer being 112 amino acids. TGF-ß is synthesized as a 390 amino acid precursor of which the mature peptide comprises the carboxyl terminal sequence (Derynck et al. 1985). This precursor sequence is very important for proper folding and disulfide bond formation of TGF-ß to ultimately generate a biologically active molecule.


Migration Agar Urea Carboxyl Serine 


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  1. Anzano MA, Roberts AB, De Larco JE, Wakefield LM, Assoian RK, Roche NS, Smith JM, Lazarus JE, Sporn MB (1985) Increased secretion of type β transforming growth factor accompanies viral transformation of cells. Mol Cell Biol 5:242–247PubMedGoogle Scholar
  2. Assoian RK, Komoriya A, Meyers CA, Miller DM, Sporn MB (1983) Transforming growth factor-beta in human platelets. J Biol Chem 258:7155–7160PubMedGoogle Scholar
  3. Bassols A, Massagué J (1988) Transforming growth factor-β regulates expression and structure of extracellular matrix chondroitin/dermatan sulfate proteoglycans. J Biol Chem 263:3039–3045PubMedGoogle Scholar
  4. Derynck R, Jarrett JA, Chen EY, Eaton DH, Bell JR, Assoian RK, Roberts AB, Sporn MB, Goeddel DV (1985) Human transforming growth factor-beta cDNA sequences and expression in tumor cell lines. Nature 316:701–705PubMedCrossRefGoogle Scholar
  5. Ignotz R, Massagué J (1986) Transforming growth factor-beta stimulates the expression of fibronectin and collagen and their incorporation into extracellular matrix. J Biol Chem 261:4337–4345PubMedGoogle Scholar
  6. Ignotz RA, Massagué J (1987) Cell adhesion protein receptors as targets for transforming growth factor-ß action. Cell 51:189–197PubMedCrossRefGoogle Scholar
  7. Laiho M, Saksela O, Andreasen PA, 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 103:2403–2410PubMedCrossRefGoogle Scholar
  8. Lyons RM, Keski-Oja J, Moses HL (1988) Proteolytic activation of latent transforming growth factor-ß from fibroblast conditioned media. J Cell Biol 106:1659–1664PubMedCrossRefGoogle Scholar
  9. Madri JA, Pratt BM, Tucker A (1988) Phenotypic modulation of endothelial cells by transforming growth factor-ß depends on the compostion and organization of the extracellular matrix. J Cell Biol 106:1375–1384PubMedCrossRefGoogle Scholar
  10. Miyazano K, Hellman U, Weinstedt C, Heldin C-H (1988) Latent high molecular weight complex of transforming growth factor βl. J Biol Chem 263:6407–6415Google Scholar
  11. Mulé JJ, Schwartz SL, Roberts AB, Sporn MB, Rosenberg SA (1988) Transforming growth factor-beta inhibits the in vitro generation of lymphokine-activated killer cells and cytoto-xic T cells. Cancer Immunol Immunother 26:95–100PubMedGoogle Scholar
  12. Pircher R, Jullien P, Lawrence DA (1986) ßTransforming growth factor is stored in human blood platelets as a latent high molecular weight complex. Biochem Biophys Res Commun 136:30–37PubMedCrossRefGoogle Scholar
  13. Postlethwaite AE, Keski-Oja J, Moses HL, Kang AH (1987) Stimulation of the chemotactic migration of human fibroblasts by transforming growth factor beta. J Exp Med 165:251–256PubMedCrossRefGoogle Scholar
  14. Roberts AB, Anzano MA, Lamb LC, Smith JM, Sporn MB (1981) New class of transforming growth factors potentiated by epidermal growth factor. Proc Natl Acad Sci USA 78:5339–5343PubMedCrossRefGoogle Scholar
  15. Roberts AB, Sporn MB, Assoian RK, Smith JM, Roche NS, Wakefield LM, Heine UI, Liotta LA, Falanga V, Kehrl JH, Fauci AS (1986) Transforming growth factor type-beta: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc Natl Acad Sci USA 83:4167–4171PubMedCrossRefGoogle Scholar
  16. Roberts AB, Flanders KC, Kondaiah P, Thompson N, Van Obberghen-Schilling E, Wake-field LM, Rossi P, de Crombrugghe B, Heine U, Sporn M (1988a) Transforming growth factor β: biochemistry and roles in embryogenesis, tissue repair and remodeling, and carcinogenesis. Recent Progress in Hormone Research 43:157–197Google Scholar
  17. Roberts AB, Thompson NL, Heine U, Flanders KC, Sporn MB (1988b) Transforming growth factor β: possible roles in carcinogenesis. Br J Cancer 57:594–600PubMedCrossRefGoogle Scholar
  18. Seyedin SM, Thomas TC, Thompson AY, Rosen DM, Piez KA (1985) Purification and characterization of two cartilage-inducing factors from bovine demineralized bone. Proc Natl Acad Sci USA 82:2267–2271PubMedCrossRefGoogle Scholar
  19. Sporn MB, Roberts AB (1988) Transforming growth factor-beta: new chemical forms and new biological roles. Biofactors 1:89–93PubMedGoogle Scholar
  20. Thompson NL, Flanders KC, Smith JM, Roberts AB, Sporn MB (1988) Cell type specific expression of transforming growth factor-beta 1 in adult and neonatal mouse tissue. J Cell Biol 108:661–669CrossRefGoogle Scholar
  21. Wakefield LM, Smith DM, Masui T, Harris CC, Sporn MB (1987) Distribution and modulation of the cellular receptor for transforming growth factor-beta. J Cell Biol 105:965–975PubMedCrossRefGoogle Scholar
  22. Wakefield LM, Smith DM, Flanders KC, Sporn MB (1988) Latent transforming growth factor-ß from human platelets. J Biol Chem 263:7646–7654PubMedGoogle Scholar
  23. Wrann M, Bodmer S, de Martin R, Siepl C, Hofer-Warbinek R, Frei K, Hofer E, Fontana A (1987) T Cell supressor factor from glioblastoma cells is a 25 kD protein closely related to transforming growth factor-beta. EMBO J 6:1633–1636PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • K. C. Flanders
    • 1
  • M. B. Sporn
    • 1
  • A. B. Roberts
    • 1
  1. 1.Laboratory of ChemopreventionNational Cancer InstituteBethesdaUSA

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