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. 1984 Feb;81(3):926–930. doi: 10.1073/pnas.81.3.926

A glioma-derived analog to platelet-derived growth factor: demonstration of receptor competing activity and immunological crossreactivity.

M Nistér, C H Heldin, A Wasteson, B Westermark
PMCID: PMC344952  PMID: 6322178

Abstract

A human clonal glioma cell line, U-343 MGa Cl 2, cultured under serum-free conditions, was found to release a factor that competed with 125I-labeled platelet-derived growth factor (125I-PDGF) for binding to human foreskin fibroblasts. The concentration of competing activity in conditioned medium was equal to 20-30 ng of PDGF per ml. The PDGF receptor competing activity had an elution position on Sephadex G-200 close to that of tracer PDGF. The same fractions in the chromatogram also contained growth-promoting activity and material active in a PDGF radioimmunoassay. Incubation of partially purified, 125I-labeled glioma factor with fibroblasts, or rabbit anti-PDGF serum, led to the selective binding of a component with an estimated Mr of 31,000, as shown by NaDodSO4/gel electrophoresis under nonreducing conditions. After reduction this component migrated as a Mr 18,000 protein. Thus, the behavior in NaDodSO4/gel electrophoresis was similar to that of PDGF. Furthermore, incubation of partially purified glioma factor with immobilized PDGF antibodies markedly decreased the amount of PDGF receptor competing activity remaining in the supernatant. These results suggest that the factor produced by glioma cells has structural, immunological, and functional resemblance to PDGF. We previously reported that a human osteosarcoma cell line produces a PDGF-like molecule with growth-promoting activity. Taken together with the recent finding that PDGF is homologous to the transforming gene product of simian sarcoma virus, our present data give additional support for the idea that an autocrine activation of the PDGF receptor may be operational in the growth of human tumors of mesenchymal or glial origin.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Antoniades H. N., Hunkapiller M. W. Human platelet-derived growth factor (PDGF): amino-terminal amino acid sequence. Science. 1983 May 27;220(4600):963–965. doi: 10.1126/science.6844921. [DOI] [PubMed] [Google Scholar]
  2. Blobel G., Dobberstein B. Transfer of proteins across membranes. I. Presence of proteolytically processed and unprocessed nascent immunoglobulin light chains on membrane-bound ribosomes of murine myeloma. J Cell Biol. 1975 Dec;67(3):835–851. doi: 10.1083/jcb.67.3.835. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bowen-Pope D. F., Ross R. Platelet-derived growth factor. II. Specific binding to cultured cells. J Biol Chem. 1982 May 10;257(9):5161–5171. [PubMed] [Google Scholar]
  4. Busch C., Wasteson A., Westermark B. Release of a cell growth promoting factor from human platelets. Thromb Res. 1976 Apr;8(4):493–500. doi: 10.1016/0049-3848(76)90227-9. [DOI] [PubMed] [Google Scholar]
  5. Bürk R. R. Induction of cell proliferation by a migration factor released from a transformed cell line. Exp Cell Res. 1976 Sep;101(2):293–298. doi: 10.1016/0014-4827(76)90380-3. [DOI] [PubMed] [Google Scholar]
  6. Currie G. A. Platelet-derived growth-factor requirements for in vitro proliferation of normal and malignant mesenchymal cells. Br J Cancer. 1981 Mar;43(3):335–343. doi: 10.1038/bjc.1981.53. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Devare S. G., Reddy E. P., Law J. D., Robbins K. C., Aaronson S. A. Nucleotide sequence of the simian sarcoma virus genome: demonstration that its acquired cellular sequences encode the transforming gene product p28sis. Proc Natl Acad Sci U S A. 1983 Feb;80(3):731–735. doi: 10.1073/pnas.80.3.731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dicker P., Pohjanpelto P., Pettican P., Rozengurt E. Similarities between fibroblast-derived growth factor and platelet-derived growth factor. Exp Cell Res. 1981 Sep;135(1):221–227. doi: 10.1016/0014-4827(81)90314-1. [DOI] [PubMed] [Google Scholar]
  9. Doolittle R. F., Hunkapiller M. W., Hood L. E., Devare S. G., Robbins K. C., Aaronson S. A., Antoniades H. N. Simian sarcoma virus onc gene, v-sis, is derived from the gene (or genes) encoding a platelet-derived growth factor. Science. 1983 Jul 15;221(4607):275–277. doi: 10.1126/science.6304883. [DOI] [PubMed] [Google Scholar]
  10. Graves D. T., Owen A. J., Antoniades H. N. Evidence that a human osteosarcoma cell line which secretes a mitogen similar to platelet-derived growth factor requires growth factors present in platelet-poor plasma. Cancer Res. 1983 Jan;43(1):83–87. [PubMed] [Google Scholar]
  11. Heldin C. H., Westermark B., Wasteson A. Chemical and biological properties of a growth factor from human-cultured osteosarcoma cells: resemblance with platelet-derived growth factor. J Cell Physiol. 1980 Nov;105(2):235–246. doi: 10.1002/jcp.1041050207. [DOI] [PubMed] [Google Scholar]
  12. Heldin C. H., Westermark B., Wasteson A. Demonstration of an antibody against platelet-derived growth factor. Exp Cell Res. 1981 Dec;136(2):255–261. doi: 10.1016/0014-4827(81)90003-3. [DOI] [PubMed] [Google Scholar]
  13. Heldin C. H., Westermark B., Wasteson A. Specific receptors for platelet-derived growth factor on cells derived from connective tissue and glia. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3664–3668. doi: 10.1073/pnas.78.6.3664. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Huang J. S., Huang S. S., Kennedy B., Deuel T. F. Platelet-derived growth factor. Specific binding to target cells. J Biol Chem. 1982 Jul 25;257(14):8130–8136. [PubMed] [Google Scholar]
  15. Johnsson A., Heldin C. H., Westermark B., Wasteson A. Platelet-derived growth factor: identification of constituent polypeptide chains. Biochem Biophys Res Commun. 1982 Jan 15;104(1):66–74. doi: 10.1016/0006-291x(82)91941-6. [DOI] [PubMed] [Google Scholar]
  16. Kaplan K. L., Broekman M. J., Chernoff A., Lesznik G. R., Drillings M. Platelet alpha-granule proteins: studies on release and subcellular localization. Blood. 1979 Apr;53(4):604–618. [PubMed] [Google Scholar]
  17. Laskey R. A., Mills A. D. Enhanced autoradiographic detection of 32P and 125I using intensifying screens and hypersensitized film. FEBS Lett. 1977 Oct 15;82(2):314–316. doi: 10.1016/0014-5793(77)80609-1. [DOI] [PubMed] [Google Scholar]
  18. Massague J., Czech M. P., Iwata K., DeLarco J. E., Todaro G. J. Affinity labeling of a transforming growth factor receptor that does not interact with epidermal growth factor. Proc Natl Acad Sci U S A. 1982 Nov;79(22):6822–6826. doi: 10.1073/pnas.79.22.6822. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Miletich J. P., Broze G. J., Jr, Majerus P. W. The synthesis of sulfated dextran beads for isolation of human plasma coagulation factors II, IX, and X. Anal Biochem. 1980 Jul 1;105(2):304–310. doi: 10.1016/0003-2697(80)90462-5. [DOI] [PubMed] [Google Scholar]
  20. Nistér M., Heldin C. H., Wasteson A., Westermark B. A platelet-derived growth factor analog produced by a human clonal glioma cell line. Ann N Y Acad Sci. 1982 Dec 10;397:25–33. doi: 10.1111/j.1749-6632.1982.tb43414.x. [DOI] [PubMed] [Google Scholar]
  21. Ross R., Vogel A. The platelet-derived growth factor. Cell. 1978 Jun;14(2):203–210. doi: 10.1016/0092-8674(78)90107-1. [DOI] [PubMed] [Google Scholar]
  22. Scher C. D., Shepard R. C., Antoniades H. N., Stiles C. D. Platelet-derived growth factor and the regulation of the mammalian fibroblast cell cycle. Biochim Biophys Acta. 1979 Aug 10;560(2):217–241. doi: 10.1016/0304-419x(79)90020-9. [DOI] [PubMed] [Google Scholar]
  23. Sporn M. B., Todaro G. J. Autocrine secretion and malignant transformation of cells. N Engl J Med. 1980 Oct 9;303(15):878–880. doi: 10.1056/NEJM198010093031511. [DOI] [PubMed] [Google Scholar]
  24. Waterfield M. D., Scrace G. T., Whittle N., Stroobant P., Johnsson A., Wasteson A., Westermark B., Heldin C. H., Huang J. S., Deuel T. F. Platelet-derived growth factor is structurally related to the putative transforming protein p28sis of simian sarcoma virus. Nature. 1983 Jul 7;304(5921):35–39. doi: 10.1038/304035a0. [DOI] [PubMed] [Google Scholar]
  25. Westermark B., Magnusson A., Heldin C. H. Effect of epidermal growth factor on membrane motility and cell locomotion in cultures of human clonal glioma cells. J Neurosci Res. 1982;8(2-3):491–507. doi: 10.1002/jnr.490080236. [DOI] [PubMed] [Google Scholar]
  26. Williams L. T., Tremble P., Antoniades H. N. Platelet-derived growth factor binds specifically to receptors on vascular smooth muscle cells and the binding becomes nondissociable. Proc Natl Acad Sci U S A. 1982 Oct;79(19):5867–5870. doi: 10.1073/pnas.79.19.5867. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Witte L. D., Kaplan K. L., Nossel H. L., Lages B. A., Weiss H. J., Goodman D. S. Studies of the release from human platelets of the growth factor for cultured human arterial smooth muscle cells. Circ Res. 1978 Mar;42(3):402–409. doi: 10.1161/01.res.42.3.402. [DOI] [PubMed] [Google Scholar]
  28. de Larco J. E., Todaro G. J. Growth factors from murine sarcoma virus-transformed cells. Proc Natl Acad Sci U S A. 1978 Aug;75(8):4001–4005. doi: 10.1073/pnas.75.8.4001. [DOI] [PMC free article] [PubMed] [Google Scholar]

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