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Growth factors: A new dimension in the unterstanding of oncogenesis

Eine neue Dimension im Verständnis der Onkogenese

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Summary

The current understanding in biology and function of 4 growth factors is reviewed. PDGF suggests functions for proto-oncogens in normal cells, which may interact in tightly linked hierachies to induce malignant growth. PDGF-requirement of normal fibroblast cell-lines is lost when the cells are infected with tumor viruses. TGF is able to stimulate growth of normally anchorage dependent cells in an anchorage independent manner in soft agar. This ability is thought to be the best in-vitro correlate of neoplastic transformation. The peptide hormones bombesin/gastrin releasing factor and EGF can act as autocrine growth factors in various lung cancer cell-lines and stimulate clonal tumor cell growth in-vitro. The potential clinical application of these types of growth factors may enable the in-vitro growth from any lung cancer patient and allow individual drug testing. TCGF produced by T-cells to activate T-cells, is central to immune stimulation and immune response. Models for potential indirect anticancer effects either by in-vivo administration or by in-vivo incubation plus passive transfer of T-cells are presented to be initiated in future clinical trials.

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Abbreviations

AIDS:

acquired immune deficiency syndrome

AS:

Aminosäuren

BC:

Bronchial Carcinoma

BN:

Bombesin

EGF:

epidermal growth factor

GRP:

gastrin releasing peptide

IL-2:

Interleukin 2

m-RNA:

messenger ribonucleic acid

NK:

natural killer (cells)

NRK:

normal rat kidney

PDGF:

platelet derived growth factor

SGF:

sarcoma growth factor

TCGF:

T-cell growth factor

TGF:

transforming growth factor

WF:

Wachstumsfaktoren

Literatur

  1. Antoniades HN, Scher CD, Stiles CD (1979) Purification of the human platelet-derived growth factor. Proc Natl Acad Sci USA 76:1809–1813

    Google Scholar 

  2. Heldin CH, Westermark B, Wasteson A (1979) Platelet derived growth factor: purification and partial characterization. Proc Natl Acad Sci USA 76:3722–3726

    Google Scholar 

  3. Doolittle RF, Hunkapiller MW, Hood LE, Devare SG, Robbins KC, Aaronson SA, Antoniades HN (1983) Simian sarcoma virus oncogene, v-sis is derived from the gene (or genes) encoding a platelet-derived growth factor. Science 221:275–276

    Google Scholar 

  4. Kelly K, Cochran BH, Stiles CD, Leder P (1983) Specific regulation of the c-myc gene by lymphocyte mitogens and platelet-derived growth factor. Cell 35:603–610

    Google Scholar 

  5. Singh JP, Chaikin MA, Stiles CD (1982) Phylogenetic analysis of platelet-derived growth factor by radio-receptor assay. J Cell Biol 97:667–671

    Google Scholar 

  6. Singh JP, Chaikin MA, Pledger WJ, Scher CD, Stiles CD (1983) Persistence of the mitogenic response to platelet-derived growth factor (competence) does not reflect a long-term interaction between the growth factor and the target cell. J Cell Biol 96:1497–1502

    Google Scholar 

  7. Cochran BH, Reffel AC, Stiles CD (1983) Molecular cloning of gene sequences regulated by platelet-derived growth factor. Cell 33:939–947

    Google Scholar 

  8. Waterfield MD, Scrace GT, Whittle N, Stroobant P, Johnsson A, Wasteson A, Westermark B, Heldin CH, Huang JS, Deuel TF (1983) Platelet derived growth factor is structurally related to the putative transforming protein p28sis of simian sarcoma virus. Nature 304:35–39

    Google Scholar 

  9. DeLarco JE, Todaro GJ (1978) Growth factors from murine sarcoma virus-transformed cells. Proc Natl Acad Sci USA 75:4001–4005

    Google Scholar 

  10. Roberts AB, Frolik CA, Anzano MA, Sporn MB (1983) Transforming growth factors from neoplastic and nonneoplastic tissues. Fed Proc 42:2621–2626

    Google Scholar 

  11. Marquardt H, Hunkapiller MW, Hood LE, Twardzik DR, DeLarco JE, Stephenson JR, Todaro GJ (1983) Transforming growth factors produced by retrovirus-transformed rodent fibroblasts and human melanoma cells: amino acid sequence homology with epidermal growth factor. Proc Natl Acad Sci USA 80:4684–4688

    Google Scholar 

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

    Google Scholar 

  13. Assoian RK, Komoriya A, Meyers CA, Miller DM, Sporn MB (1983) Transforming growth factor-β in human platelets. J Biol Chem 258:7155–7160

    Google Scholar 

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

    Google Scholar 

  15. Assoian RK, Frolik CA, Roberts AB, Miller DM, Sporn MB (1984) Transforming growth factor-beta controls receptor levels for epidermal growth factor in NRK fibroblasts. Cell 36:35–41

    Google Scholar 

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

    Google Scholar 

  17. Roberts A, Frolik C, Anzaro M, Sporn M (1983) Federation Proc 42:2621

    Google Scholar 

  18. Roberts AB, Anzano MA, Lamb LC, Smith JM, 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 

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

    Google Scholar 

  20. Carney DN, Brunn PA, Gazdar AF, Pagan JF, Minna JD (1981) Selective growth in serum-free hormone-supplemented medium of tumor cells obtained by biopsy from patients with small cell carcinoma of the lung. Proc Nat Acad Sci USA 78:3158–3189

    Google Scholar 

  21. Minna JD, Carney DN, Oie H, Bunn PA Jr, Gazudar AF (1982) In: Sato G, Pardee A (eds) Cold Spring Harbor Conference on Cell Proliferation. Vol 9, Cold Spring Harbor N.Y., pp 627–639

  22. Moody TW, Pert CB, Gazdar AF, Carney DN, Minna JD (1981) High levels of intracellular bombesin characterize human small-cell lung carcinoma. Science 214:1246–1248

    Google Scholar 

  23. Carpenter G (1983) The biochemistry and physiology of the receptor-kinase for epidermal growth factor. Molec Cell Endocrinol 31:1–19

    Google Scholar 

  24. Carpenter G, Cohen S (1976) 1251-labeled human epidermal growth factor. Binding, internalization, and degradation in human fibrobalsts. J Cell Biol 71:159–171

    Google Scholar 

  25. Stoscheck CM, Carpenter G (1984) Down regulation of epidermal growth factor receptors: direct demonstration of receptor degradation in human fibrobalsts. J Cell Biol 98:1048–1053

    Google Scholar 

  26. Carpenter G, Stoscheck CM, Preston YA, DeLarco JE (1983) Antibodies to the epidermal growth factor receptor block the biological activities of sarcoma growth factor. Proc Natl Acad Sci USA 80:5627–5630

    Google Scholar 

  27. Morgan DA, Rucetti FW (1976) Selective in vitro growth of T-lymphocytes from normal bone marrows. Science 193:1007–1008

    Google Scholar 

  28. Welte K, Wang CY, Mertelsmann R, Ventun S, Feldmann SP, Moore MA (1982) Purification of human interleukin 2 to apparent homogeneity and its molecular heterogeneity. J Exp Med 156:454–464

    Google Scholar 

  29. Meuer SC, Hussey RE, Penta AC, Fitzgerald KA, Stadler BM, Schlonmann SF, Reinherz EL (1982) Cellular origin of Interleukin 2 (IL-2) in man: evidence for stimulus restricted IL-2-production by T4+ and T8+ T-Lymphocytes. J Immunol 129:1076–1079

    Google Scholar 

  30. Taniguchi T, Matsui H, Fujita T, Takonka C, Kashima N, Yoshimoto R, Hamnro J (1983) Structure and expression of a cloned cDNA from human interleukin 2. Nature 302:305–310

    Google Scholar 

  31. Wagner H, Röllinghoff M (1978) T-T-cell interactions during in vitro cytotoxic allograft response. I. Soluble products from activated Ly1+T cells trigger autonomously antigenprimed Ly23+T cells to cell proliferation and cytolytic activity. J Exp Med 148:1423–1538

    Google Scholar 

  32. Farrar JJ, Mizel SB, Fuller-Farrar J, Farrar WL, Hilfiker ML (1980) Macrophage-independent activation of helper T-cells. I. Production of Interleukin 2. J Immunol 125:793

    Google Scholar 

  33. Grimm EA, Mazumder A, Zhang HZ, Rosenberg SA (1982) Lymphokine-activated killer cell phenomenon. Lysis of natural killer-resistant fresh solid tumor cells by interleukin-2-activated autologous human peripheral blood lymphocytes. J Exp Med 155:1823–1841

    Google Scholar 

  34. Domzig W, Stadler BM, Herbermann RB (1983) Interleukin 2 dependence of human natural killer (NK) cell activity. J Immunol 130:1973

    Google Scholar 

  35. Gillis S, Crabtree GR, Smith KA (1979) Glucocorticoid-induced inhibition of T cell growth factor production. In: The effect on mitogen-induced lymphocyte proliferation. J Immunol 123:1624

    Google Scholar 

  36. Palacios R, Möller G (1982) Cyclosporin A blocks receptors for HLA-DR antigens on T-cells. Nature 290:792

    Google Scholar 

  37. Flomenberg N, Welte K, Merklmann R, O'Reilly R, Dupont B (1983) Interleukin 2-dependent natural killer (NK) cell lines from patients with primary T-cell immuno-deficiencies. J Immunol 130:2635–2643

    Google Scholar 

  38. Rook AH, Masur H, Lane HC, Frederick W, Kasahara T, Mader AM, Djeu IY, Manischewitz IF, Jackson L, Fanci AS, Quinnan GV Jr (1983) Interleukin 2 enhances the depressed natural killer and cytomegalovirus-specific cytotoxic activities of lymphocytes from patients with acquired immune deficiency-syndrome. J Clin Inv 72:398–403

    Google Scholar 

  39. Lotze MT, Line BR, Mathisen DJ, Rosenberg SA (1980) The in vivo distribution of autologous human and marine lymphoid cells grown in T cell growth factor (TCGF): implications for the adoptive immunotherapy of tumors. I Immunol 125:1487

    Google Scholar 

  40. Cheever MA, Greenberg PD, Fefer A, Gillis S (1982) Augmentation of the antitumor therapeutic efficacy of long-term cultured lymphocytes by in-vivo administration of purified interleukin 2. J Exp Med 155:968

    Google Scholar 

  41. Oldham RK (1984) IL-2: Potential for use in cancer treatment. In: New Biological Approaches in the Treatment of Cancer. p. 47 Bostrum Management Co. Education Symposium and Educational Workshop Booklet, 20th annual meeting of the Amer Soc Clin Oncol 1984

  42. Holley RW, Böhlen P (1980) Purification of kidney epithelial cell growth inhibitors. Proc Nat Acad Sci USA 77:5989–5992

    Google Scholar 

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

    Google Scholar 

  44. Tucker RF, Branum EL, Shipley GD, Ryan RJ, Moses HL (1984) Specific binding to cultured cells of 1251-labeled type beta transforming growth factor from human platelets. Proc Nat Acad Sci USA 81:6757–6761

    Google Scholar 

  45. Sporn MB, Roberts AB (1985)f Autocrine growth factors and cancer. Nature 313:745–747

    Google Scholar 

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Authors and Affiliations

  1. Medizinische Klinik III, Klinikum Großhadern, Ludwig-Maximilians-Universität München, Germany

    V. Heinemann & U. Jehn

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  1. V. Heinemann
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  2. U. Jehn
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Heinemann, V., Jehn, U. Wachstumsfaktoren. Klin Wochenschr 63, 740–746 (1985). https://doi.org/10.1007/BF01733825

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  • DOI: https://doi.org/10.1007/BF01733825

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