Cellular transformation by coordinated action of three peptide growth factors from human platelets

Abstract

Platelet-derived growth factor1–4 (PDGF) is known to be involved in regulating the mitosis of connective tissue cells, and recent studies have also shown that it may function in mediating cellular transformation5–8. The oncogene carried by simian sarcoma virus, sis, is homologous to one chain of PDGF5–8, and treatment of non-neoplastic cells with this growth factor results in increased transcription of another oncogene, myc (ref. 9). PDGF also stimulates the synthesis of proteins that are characteristic of transformed cells10. However, phenotypic transformation does not appear to result from the action of PDGF alone. For example, expression of myc does not transform cells in the absence of other oncogene expression11. We have recently shown that platelets contain another peptide growth factor, transforming growth factor-β (TGF-β)12,13, in addition to PDGF. We report here that extracts of human platelets can induce anchorage-independent growth of non-neoplastic rat kidney (NRK) fibroblasts, but that purified PDGF alone does not elicit this effect. Rather, the transforming activity of the platelet extract is due to a concerted action of three distinct peptides: PDGF, TGF-β and a newly identified analogue of epidermal growth factor (EGF).

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1

    Ross, R., Glomset, J., Kariya, B. & Harker, L. Proc. natn. Acad. Sci. U.S.A. 71, 1207–1210 (1974).

    ADS  CAS  Article  Google Scholar 

  2. 2

    Kohler, N. & Lipton, A. Expl Cell Res. 87, 297–301 (1974).

    CAS  Article  Google Scholar 

  3. 3

    Antoniades, H. N., Stathakos, D. & Scher, C. D. Proc. natn. Acad. Sci. U.S.A. 72, 2635–2639 (1975).

    ADS  CAS  Article  Google Scholar 

  4. 4

    Antoniades, H. N. & Scher, C. D. Proc. natn. Acad. Sci. U.S.A. 74, 1973–1977 (1977).

    ADS  CAS  Article  Google Scholar 

  5. 5

    Waterfield, M. D. et al. Nature 304, 35–39 (1983).

    ADS  CAS  Article  Google Scholar 

  6. 6

    Doolittle, R. F. et al. Science 221, 275–277 (1983).

    ADS  CAS  Article  Google Scholar 

  7. 7

    Robbins, K. C., Antoniades, H. N., Devare, S. G., Hunkapiller, M. W. & Aaronson, S. A. Nature 305, 605–608 (1983).

    ADS  CAS  Article  Google Scholar 

  8. 8

    Deuel, T. F., Huang, J. S., Huang, S. S., Stroobant, P. & Waterfield, M. D. Science 221, 1348–1350 (1983).

    ADS  CAS  Article  Google Scholar 

  9. 9

    Kelly, K., Cochran, B. H., Stiles, C. D. & Leder, P. Cell 35, 603–610 (1983).

    CAS  Article  Google Scholar 

  10. 10

    Scher, C. D., Dick, R. L., Whipple, A. P. & Locatell, K. L. Molec. Cell. Biol. 3, 70–81 (1983).

    CAS  Article  Google Scholar 

  11. 11

    Land, H., Parada, L. F. & Weinberg, R. A. Nature 304, 596–602 (1983).

    ADS  CAS  Article  Google Scholar 

  12. 12

    Assoian, R. K., Komoriya, A., Meyers, C. A., Miller, D. M. & Sporn, M. B. J. biol. Chem. 258, 7155–7160 (1983).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. 13

    Childs, C. B., Proper, J. A., Tucker, R. F. & Moses, H. L. Proc. natn. Acad. Sci. U.S.A. 79, 5312–5316 (1982).

    ADS  CAS  Article  Google Scholar 

  14. 14

    Kahn, P. & Shin, S. J. Cell Biol. 82, 1–16 (1979).

    CAS  Article  Google Scholar 

  15. 15

    De Larco, J. E. & Todaro, G. J. Proc. natn. Acad. Sci. U.S.A. 75, 4001–4005 (1978).

    ADS  CAS  Article  Google Scholar 

  16. 16

    Antoniades, H. N., Scher, C. D. & Stiles, C. D. Proc. natn. Acad. Sci. U.S.A. 76, 1809–1813 (1979).

    ADS  CAS  Article  Google Scholar 

  17. 17

    Roberts, A. B., Frolik, C. A., Anzano, M. A. & Sporn, M. B. Fedn Proc. 42, 2621–2626 (1983).

    CAS  Google Scholar 

  18. 18

    Roberts, A. B., Anzano, M. A., Lamb, L. C., Smith, J. M. & Sporn, M. B. Proc. natn. Acad. Sci. U.S.A. 78, 5339–5343 (1981).

    ADS  CAS  Article  Google Scholar 

  19. 19

    Laemmli, U. K. Nature 227, 680–685 (1970).

    ADS  CAS  Article  Google Scholar 

  20. 20

    Roberts, A. B. et al. Biochemistry 22, 5692–5698 (1983).

    CAS  Article  Google Scholar 

  21. 21

    Taylor, J. M., Cohen, S. & Mitchell, W. M. Proc. natn. Acad. Sci. U.S.A. 67, 164–171 (1970).

    ADS  CAS  Article  Google Scholar 

  22. 22

    Taylor, J. M., Mitchell, W. M. & Cohen, S. J. biol. Chem. 249, 3198–3203 (1974).

    CAS  PubMed  Google Scholar 

  23. 23

    Bowen-Pope, D. F., DiCorleto, P. E. & Ross, R. J. Cell Biol. 96, 679–683 (1983).

    CAS  Article  Google Scholar 

  24. 24

    Collins, M. K. L., Sinnett-Smith, J. W. & Rozengurt, E. J. biol. Chem. 258, 11689–11693 (1983).

    CAS  PubMed  Google Scholar 

  25. 25

    Fabricant, R. N., De Larco, J. E. & Todaro, G. J. Proc. natn. Acad. Sci. U.S.A. 74, 565–569 (1977).

    ADS  CAS  Article  Google Scholar 

  26. 26

    Heldin, C.-H., Westermark, B. & Wasteson, Å. Proc. natn. Acad. Sci. U.S.A. 78, 3664–3668 (1981).

    ADS  CAS  Article  Google Scholar 

  27. 27

    Bowen-Pope, D. F. & Ross, R. J. biol. Chem. 257, 5161–5171 (1982).

    CAS  PubMed  Google Scholar 

  28. 28

    Oka, Y. & Orth, D. N. J. clin. Invest. 72, 249–259 (1983).

    CAS  Article  Google Scholar 

  29. 29

    Schechter, Y., Hernaez, L., Schlessinger, J. & Cuatrecasas, P. Nature 278, 835–838 (1979).

    ADS  CAS  Article  Google Scholar 

  30. 30

    Schreiber, A. B., Yarden, Y. & Schlessinger, J. Biochem. biophys. Res. Commun. 101, 517–523 (1981).

    CAS  Article  Google Scholar 

  31. 31

    Stiles, C. D. et al. Proc. natn. Acad. Sci. U.S.A. 76, 1279–1283 (1979).

    ADS  CAS  Article  Google Scholar 

  32. 32

    Clemmons, D. R., Van Wyk, J. J. & Pledger, W. J. Proc. natn. Acad. Sci. U.S.A. 77, 6644–6648 (1980).

    ADS  CAS  Article  Google Scholar 

  33. 33

    Wharton, W., Leof, E., Olashaw, N., O'Keefe, E. J. & Pledger, W. J. Expl Cell Res. 147, 443–448 (1983).

    CAS  Article  Google Scholar 

  34. 34

    Assoian, R. K., Frolik, C. A., Roberts, A. B., Miller, D. M. & Sporn, M. B. Cell 36, 35–41 (1984).

    CAS  Article  Google Scholar 

  35. 35

    Gregory, H. Nature 257, 325–327 (1975).

    ADS  CAS  Article  Google Scholar 

  36. 36

    Savage, C. R., Inagami, T. & Cohen, S. J. biol. Chem. 247, 7612–7621 (1972).

    CAS  Google Scholar 

  37. 37

    Marquardt, H. et al. Proc. natn. Acad. Sci. U.S.A. 80, 4684–4688 (1983).

    ADS  CAS  Article  Google Scholar 

  38. 38

    Massagué, J. J. biol. Chem. 258, 13606–13613 (1983).

    PubMed  Google Scholar 

  39. 39

    Gray, A., Dull, T. J. & Ullrich, A. Nature 303, 722–725 (1983).

    ADS  CAS  Article  Google Scholar 

  40. 40

    Scott, J. et al. Science 221, 236–240 (1983).

    ADS  CAS  Article  Google Scholar 

  41. 41

    Roberts, A. B. et al. Proc. natn. Acad. Sci. U.S.A. 77, 3494–3498 (1980).

    ADS  CAS  Article  Google Scholar 

  42. 42

    Savage, C. R. & Cohen, S. J. biol. Chem. 247, 7609–7611 (1972).

    CAS  Google Scholar 

  43. 43

    Cohen, S. & Carpenter, G. Proc. natn. Acad. Sci. U.S.A. 72, 1317–1321 (1975).

    ADS  CAS  Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Assoian, R., Grotendorst, G., Miller, D. et al. Cellular transformation by coordinated action of three peptide growth factors from human platelets. Nature 309, 804–806 (1984). https://doi.org/10.1038/309804a0

Download citation

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.