Skip to main content
SpringerLink
Log in

Role of PDGF-Like Growth Factors in Autocrine Stimulation of Growth of Normal and Transformed Cells

  • Chapter
Oncogenes and Growth Control

Abstract

The normal cellular homologs of several retroviral oncogenes have recently been identified as structural genes for proteins which are proven or thought to play a role in mitogenesis. It is therefore likely that the viral oncogene products stimulate uncontrolled cell proliferation by subverting the mitogenic pathway at key regulatory points. An indication that similar mechanisms may operate in nonviral cell transformation comes from the old observation that cell lines established from malignant tumors grow more or less independently of exogenously added growth factors. One possibility, which is supported by recent experimental data, is that transformed cells may produce growth factors that stimulate their own growth in an autocrine manner. This review focuses on platelet-derived growth factor (PDGF) and related factors and their possible role in autocrine and paracrine mechanisms in both normal and transformed cells.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Barrett TB, Gajdusek C, Schwartz SM, McDougall JK, Benditt EP (1984) Expression of the sis gene by endothelial cells in culture and in vitro. Proc Natl Acad Sci USA 81: 6772–6774

    Article  CAS  PubMed  Google Scholar 

  • Betsholtz C, Heldin C-H, Nistér M, Ek B, Wasteson A, Westermark B (1983) Synthesis of a PDGF-like growth factor in human glioma and sarcoma cells suggests the expression of the cellular homologue of the transforming protein of simian sarcoma virus. Biochem Biophys Res Commun 117: 176–182

    Article  CAS  PubMed  Google Scholar 

  • Betsholtz C, Westermark B, Ek B, Heldin C-H (1984) Co-expression of a PDGF-like growth factor and PDGF receptors in a human osteosarcoma cell line: implications for autocrine receptor activation. Cell 39: 447–457

    Article  CAS  PubMed  Google Scholar 

  • Betsholtz C, Johnsson A, Heldin C-H, Westermark B, Lind P, Urdea MS, Eddy R, Shows TB, Philpott K, Mellor A, Knott TJ, Scott J (1986) cDNA sequence and chromosomal localization of human platelet-derived growth factor A chain and its expression in tumor cell lines. Nature 320:695–699

    Article  CAS  PubMed  Google Scholar 

  • Bowen-Pope DF, Vogel A, Ross R (1984) Production of platelet-derived growth factor-like molecules and reduced expression of platelet-derived growth factor receptors accompany transformation by a wide spectrum of agents. Proc Natl Acad Sci USA 81: 2396–2400

    Article  CAS  PubMed  Google Scholar 

  • Chiu I-M, Reddy EP, Givol D, Robbins KC, Tronick SR, Aaronson SA (1984) Nucleotide sequence analysis identifies the human c-sis proto-oncogene as a structural gene for platelet-derived growth factor. Cell 37: 123–129

    Article  CAS  PubMed  Google Scholar 

  • Collins T, Ginsburg D, Boss JM, Orkin SH, Pober JS (1985) Cultured human endothelial cells express platelet-derived growth factor B chains: cDNA cloning and structural analysis. Nature 316: 748–750

    Article  CAS  PubMed  Google Scholar 

  • Deinhardt F (1980) Biology of primate retroviruses. In: Klein G (ed) Viral oncology. Raven, New York, pp 357–398

    Google Scholar 

  • Doolittle RF, Hunkapiller MW, Hood LE, Devare SG, Robbins KC, Aaronson SA, Antoniades HN (1983) Simian sarcoma virus one-gene, v-sis, is derived from the gene (or genes) encoding a platelet-derived growth factor. Science 221: 275–277

    Article  CAS  PubMed  Google Scholar 

  • Gazit A, Igarashi H, Chiu I-M, Srinivasan A, Yaniv A, Tronick SR, Robbins KC, Aaronson SA (1984) Expression of the normal human sis/PDGF-2 coding sequence induces cellular transformation. Cell 39: 80–97

    Article  Google Scholar 

  • Goustin AS, Betsholtz C, Pfeiffer-Ohlsson S, Persson H, Rydnert J, Bywater M, Holmgren G, Heldin C-H, Westermark B, Ohlsson R (1985) Co-expression of the sis and myc protooncogenes in human placenta suggests autocrine control of trophoblast growth. Cell 41: 301–312

    Article  CAS  PubMed  Google Scholar 

  • Hannink M, Donoghue DJ (1984) Requirement for a signal sequence in biological expression of the v-sis oncogene. Science 226: 1197–1199

    Article  CAS  PubMed  Google Scholar 

  • Heldin C-H, Westermark B, Wasteson A (1980) Chemical and biological properties of a growth factor from human cultured osteosarcoma cells: resemblance with platelet-derived growth factor. J Cell Physiol 105: 235–246

    Article  CAS  PubMed  Google Scholar 

  • Heldin C-H, Wasteson A, Westermark B (1985) Platelet-derived growth factor. Mol Cell Endocr 39: 169–187

    Article  CAS  Google Scholar 

  • Heldin C-H, Betsholtz C, Johnsson A, Westermark B (1986a) Role of PDGF-like growth factors in malignant transformation. Cancer Rev (in press)

    Google Scholar 

  • Heldin C-H, Johnsson A, Wennergren S, Wernstedt C, Betsholtz C, Westermark B (1986b) A human osteosarcoma cell line secretes a growth factor structurally related to a homodimer of PDGF A chains. Nature 319: 511–514

    Article  CAS  PubMed  Google Scholar 

  • Johnsson A, Heldin C-H, Wasteson A, Westermark B, Deuel TF, Huang JS, Seeburg PH, Gray E, Ullrich A, Scarce G, Stroobant P, Waterfield MD (1984) The c-sis gene encodes a precursor of the B chain of platelet-derived growth factor. EMBO J 3: 921–928

    CAS  PubMed  Google Scholar 

  • Johnsson A, Betsholtz C, Heldin C-H, Westermark B (1985) Antibodies to platelet-derived growth factor inhibit acute transformation by simian sarcoma virus. Nature 317: 438–440

    Article  CAS  PubMed  Google Scholar 

  • Josephs SF, Guo C, Ratner L, Wong-Staal F (1984a) Human proto-oncogene nucleotide sequences corresponding to the transforming region of simian sarcoma virus. Science 223: 487–491

    Article  CAS  PubMed  Google Scholar 

  • Josephs SF, Ratner L, Clarke MF, Westin EH, Reitz MS, Wong-Staal F (1984b) Transforming potential of human c-sis nucleotide sequences encoding platelet-derived growth factor. Science 225: 636–639

    Article  CAS  PubMed  Google Scholar 

  • Kelly JD, Raines EW, Ross R, Murray MJ (1985) The B chain of PDGF alone is sufficient for mitogenesis. EMBO J 4: 3399–3405

    CAS  PubMed  Google Scholar 

  • King CR, Giese NA, Robbins KC, Aaronson SA (1985) In vitro mutagenesis of the v-sis transforming gene defines functional domains of its growth factor-related product. Proc Natl Acad Sci USA 82: 5295–5299

    Article  CAS  PubMed  Google Scholar 

  • Martinet Y, Bitterman PB, Mornex J-F, Grotendorst G, Martin GR, Crystal RG (1985) Activated human monocytes express the c-sis proto-oncogene and release a mediator showing PDGF-like activity. Nature 319: 158–160

    Article  Google Scholar 

  • Nilsson J, Sjölund M, Palmberg L, Thyberg J, Heldin C-H (1985) Arterial smooth muscle cells in primary culture produce a platelet-derived growth factor-like protein. Proc Natl Acad Sci USA 82: 4418–4422

    Article  CAS  PubMed  Google Scholar 

  • Nistér M, Heldin C-H, Wasteson A, Westermark B (1984) A glioma-derived analog to platelet-derived growth factor: demonstration of receptor competing activity and immunological cross-reactivity. Proc Natl Acad Sci USA 81: 926–930

    Article  PubMed  Google Scholar 

  • Nistér M, Heldin C-H, Westermark B (1986) Clonal variation in the production of a PDGF-like growth factor and expression of PDGF receptors in a human malignant glioma. Cancer Res 46: 332–340

    PubMed  Google Scholar 

  • Robbins KC, Antoniades HN, Devare SG, Hunkapiller MW, Aaronson SA (1983) Structural and immunological similarities between simian sarcoma virus gene product(s) and human platelet-derived growth factor. Nature 305: 605–608

    Article  CAS  PubMed  Google Scholar 

  • Robbins KC, Leal F, Pierce JH, Aaronson SA (1985) The v-sis/PDGF-2 transforming gene product localizes to cell membranes but is not a secretory protein. EMBO J 4: 1783–1792

    CAS  PubMed  Google Scholar 

  • Rozengurt E, Sinnett-Smith J, Taylor-Papadimitriou J (1985) Production of PDGF-like growth factor by breast cancer cell lines. Int J Cancer 36: 247–252

    Article  CAS  PubMed  Google Scholar 

  • Seifert RA, Schwartz SM, Bowen-Pope DF (1984) Developmental regulation of production of platelet-derived growth factor-like molecules. Nature 311: 669–671

    Article  CAS  PubMed  Google Scholar 

  • Shimokado K, Raines ER, Madtes DK, Barrett TB, Benditt E, Ross R (1985) A significant part of macrophage-derived growth factor consists of at least two forms of PDGF. Cell 43: 277–286

    Article  CAS  PubMed  Google Scholar 

  • Stroobant P, Waterfield MD (1984) Purification and properties of porcine platelet-derived growth factor. EMBO J 2: 2963–2967

    Google Scholar 

  • van Zoelen EJJ, van de Ven WJM, Franssen HJ, van Oostwaard TMJ, van der Saag PT, Heldin C-H, de Laat SW (1985) Neuroblastoma cells express c-sis and produce a transforming growth factor antigenitally related to the platelet-derived growth factor. Mol Cell Biol 5: 2289–2297

    Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

Download references

Authors
  1. Carl-Henrik Heldin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bengt Westermark
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. European Molecular Biology Laboratory, Postfach 10 22 09, 6900, Heidelberg, Germany

    Patricia Kahn  & Thomas Graf  & 

Rights and permissions

Reprints and permissions

Copyright information

© 1986 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Heldin, CH., Westermark, B. (1986). Role of PDGF-Like Growth Factors in Autocrine Stimulation of Growth of Normal and Transformed Cells. In: Kahn, P., Graf, T. (eds) Oncogenes and Growth Control. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-73325-3_6

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-73325-3_6

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-18760-8

  • Online ISBN: 978-3-642-73325-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation