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. 1987 Jun;6(6):1627–1632. doi: 10.1002/j.1460-2075.1987.tb02410.x

An angiogenic growth factor is expressed in human glioma cells.

T A Libermann, R Friesel, M Jaye, R M Lyall, B Westermark, W Drohan, A Schmidt, T Maciag, J Schlessinger
PMCID: PMC553534  PMID: 3301330

Abstract

Progression to increased malignancy frequently occurs in human brain tumors of glial origin and usually involves neovascularization--a massive proliferation of endothelial cells into the tumor tissue. We have shown previously that subversion of a normal growth factor-related pathway is frequently associated with human gliomas. Here we show that human glioma cell lines express the gene encoding the angiogenic peptide endothelial cell growth factor (ECGF) or acidic fibroblast growth factor (a-FGF) and that an ECGF-like polypeptide is produced by these cells. The glioma-derived growth factor was partially purified from cell extracts by heparin-Sepharose affinity chromatography where it eluted at 1.5 M sodium chloride. On reversed-phase h.p.l.c., growth factor activity for endothelial cells was eluted at the same concentration of acetonitrile as found for bovine brain-ECGF, also a potent mitogen for endothelial cells. Moreover, human glioma cells possess specific cell surface receptors for ECGF and are mitogenically stimulated by exogenous addition of this growth factor. Glioma derived-ECGF may therefore have a dual influence: first, by autocrine growth-stimulation of human gliomas and, second, by paracrine-stimulation of endothelial cell proliferation which results in neovascularization of the tumor tissue.

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Selected References

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  1. Abraham J. A., Mergia A., Whang J. L., Tumolo A., Friedman J., Hjerrild K. A., Gospodarowicz D., Fiddes J. C. Nucleotide sequence of a bovine clone encoding the angiogenic protein, basic fibroblast growth factor. Science. 1986 Aug 1;233(4763):545–548. doi: 10.1126/science.2425435. [DOI] [PubMed] [Google Scholar]
  2. Betsholtz C., Johnsson A., Heldin C. H., Westermark B., Lind P., Urdea M. S., Eddy R., Shows T. B., Philpott K., Mellor A. L. cDNA sequence and chromosomal localization of human platelet-derived growth factor A-chain and its expression in tumour cell lines. Nature. 1986 Apr 24;320(6064):695–699. doi: 10.1038/320695a0. [DOI] [PubMed] [Google Scholar]
  3. Burgess W. H., Mehlman T., Friesel R., Johnson W. V., Maciag T. Multiple forms of endothelial cell growth factor. Rapid isolation and biological and chemical characterization. J Biol Chem. 1985 Sep 25;260(21):11389–11392. [PubMed] [Google Scholar]
  4. Burgess W. H., Mehlman T., Marshak D. R., Fraser B. A., Maciag T. Structural evidence that endothelial cell growth factor beta is the precursor of both endothelial cell growth factor alpha and acidic fibroblast growth factor. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7216–7220. doi: 10.1073/pnas.83.19.7216. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Carlsson J., Nilsson K., Westermark B., Pontén J., Sundström C., Larsson E., Bergh J., Påhlman S., Busch C., Collins V. P. Formation and growth of multicellular spheroids of human origin. Int J Cancer. 1983 May 15;31(5):523–533. doi: 10.1002/ijc.2910310502. [DOI] [PubMed] [Google Scholar]
  6. Derynck R. Transforming growth factor-alpha: structure and biological activities. J Cell Biochem. 1986;32(4):293–304. doi: 10.1002/jcb.240320406. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Downward J., Yarden Y., Mayes E., Scrace G., Totty N., Stockwell P., Ullrich A., Schlessinger J., Waterfield M. D. Close similarity of epidermal growth factor receptor and v-erb-B oncogene protein sequences. Nature. 1984 Feb 9;307(5951):521–527. doi: 10.1038/307521a0. [DOI] [PubMed] [Google Scholar]
  9. Esch F., Baird A., Ling N., Ueno N., Hill F., Denoroy L., Klepper R., Gospodarowicz D., Böhlen P., Guillemin R. Primary structure of bovine pituitary basic fibroblast growth factor (FGF) and comparison with the amino-terminal sequence of bovine brain acidic FGF. Proc Natl Acad Sci U S A. 1985 Oct;82(19):6507–6511. doi: 10.1073/pnas.82.19.6507. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fabricant R. N., De Larco J. E., Todaro G. J. Nerve growth factor receptors on human melanoma cells in culture. Proc Natl Acad Sci U S A. 1977 Feb;74(2):565–569. doi: 10.1073/pnas.74.2.565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Folkman J., Klagsbrun M. Angiogenic factors. Science. 1987 Jan 23;235(4787):442–447. doi: 10.1126/science.2432664. [DOI] [PubMed] [Google Scholar]
  12. Folkman J. Tumor angiogenesis. Adv Cancer Res. 1985;43:175–203. doi: 10.1016/s0065-230x(08)60946-x. [DOI] [PubMed] [Google Scholar]
  13. Goldstein G. W., Betz A. L. The blood-brain barrier. Sci Am. 1986 Sep;255(3):74–83. doi: 10.1038/scientificamerican0986-74. [DOI] [PubMed] [Google Scholar]
  14. Huang S. S., Huang J. S. Association of bovine brain-derived growth factor receptor with protein tyrosine kinase activity. J Biol Chem. 1986 Jul 25;261(21):9568–9571. [PubMed] [Google Scholar]
  15. Jaye M., Howk R., Burgess W., Ricca G. A., Chiu I. M., Ravera M. W., O'Brien S. J., Modi W. S., Maciag T., Drohan W. N. Human endothelial cell growth factor: cloning, nucleotide sequence, and chromosome localization. Science. 1986 Aug 1;233(4763):541–545. doi: 10.1126/science.3523756. [DOI] [PubMed] [Google Scholar]
  16. Klagsbrun M., Sasse J., Sullivan R., Smith J. A. Human tumor cells synthesize an endothelial cell growth factor that is structurally related to basic fibroblast growth factor. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2448–2452. doi: 10.1073/pnas.83.8.2448. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Libermann T. A., Nusbaum H. R., Razon N., Kris R., Lax I., Soreq H., Whittle N., Waterfield M. D., Ullrich A., Schlessinger J. Amplification, enhanced expression and possible rearrangement of EGF receptor gene in primary human brain tumours of glial origin. Nature. 1985 Jan 10;313(5998):144–147. doi: 10.1038/313144a0. [DOI] [PubMed] [Google Scholar]
  18. Libermann T. A., Razon N., Bartal A. D., Yarden Y., Schlessinger J., Soreq H. Expression of epidermal growth factor receptors in human brain tumors. Cancer Res. 1984 Feb;44(2):753–760. [PubMed] [Google Scholar]
  19. Maciag T., Mehlman T., Friesel R., Schreiber A. B. Heparin binds endothelial cell growth factor, the principal endothelial cell mitogen in bovine brain. Science. 1984 Aug 31;225(4665):932–935. doi: 10.1126/science.6382607. [DOI] [PubMed] [Google Scholar]
  20. Nistér M., Heldin C. H., Wasteson A., Westermark B. A glioma-derived analog to platelet-derived growth factor: demonstration of receptor competing activity and immunological crossreactivity. Proc Natl Acad Sci U S A. 1984 Feb;81(3):926–930. doi: 10.1073/pnas.81.3.926. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Pontén J., Westermark B. Properties of human malignant glioma cells in vitro. Med Biol. 1978 Aug;56(4):184–193. [PubMed] [Google Scholar]
  22. Rubinstein L. J., Herman M. M., VanderBerg S. R. Differentiation and anaplasia in central neuroepithelial tumors. Prog Exp Tumor Res. 1984;27:32–48. doi: 10.1159/000408221. [DOI] [PubMed] [Google Scholar]
  23. Schechter A. L., Stern D. F., Vaidyanathan L., Decker S. J., Drebin J. A., Greene M. I., Weinberg R. A. The neu oncogene: an erb-B-related gene encoding a 185,000-Mr tumour antigen. Nature. 1984 Dec 6;312(5994):513–516. doi: 10.1038/312513a0. [DOI] [PubMed] [Google Scholar]
  24. Schreiber A. B., Kenney J., Kowalski W. J., Friesel R., Mehlman T., Maciag T. Interaction of endothelial cell growth factor with heparin: characterization by receptor and antibody recognition. Proc Natl Acad Sci U S A. 1985 Sep;82(18):6138–6142. doi: 10.1073/pnas.82.18.6138. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Schreiber A. B., Libermann T. A., Lax I., Yarden Y., Schlessinger J. Biological role of epidermal growth factor-receptor clustering. Investigation with monoclonal anti-receptor antibodies. J Biol Chem. 1983 Jan 25;258(2):846–853. [PubMed] [Google Scholar]
  26. Schreiber A. B., Winkler M. E., Derynck R. Transforming growth factor-alpha: a more potent angiogenic mediator than epidermal growth factor. Science. 1986 Jun 6;232(4755):1250–1253. doi: 10.1126/science.2422759. [DOI] [PubMed] [Google Scholar]
  27. Shapiro J. R., Shapiro W. R. Clonal tumor cell heterogeneity. Prog Exp Tumor Res. 1984;27:49–66. [PubMed] [Google Scholar]
  28. Sherr C. J., Rettenmier C. W., Sacca R., Roussel M. F., Look A. T., Stanley E. R. The c-fms proto-oncogene product is related to the receptor for the mononuclear phagocyte growth factor, CSF-1. Cell. 1985 Jul;41(3):665–676. doi: 10.1016/s0092-8674(85)80047-7. [DOI] [PubMed] [Google Scholar]
  29. Shing Y., Folkman J., Sullivan R., Butterfield C., Murray J., Klagsbrun M. Heparin affinity: purification of a tumor-derived capillary endothelial cell growth factor. Science. 1984 Mar 23;223(4642):1296–1299. doi: 10.1126/science.6199844. [DOI] [PubMed] [Google Scholar]
  30. Taylor J. M., Illmensee R., Summers J. Efficeint transcription of RNA into DNA by avian sarcoma virus polymerase. Biochim Biophys Acta. 1976 Sep 6;442(3):324–330. doi: 10.1016/0005-2787(76)90307-5. [DOI] [PubMed] [Google Scholar]
  31. Thomas K. A., Rios-Candelore M., Giménez-Gallego G., DiSalvo J., Bennett C., Rodkey J., Fitzpatrick S. Pure brain-derived acidic fibroblast growth factor is a potent angiogenic vascular endothelial cell mitogen with sequence homology to interleukin 1. Proc Natl Acad Sci U S A. 1985 Oct;82(19):6409–6413. doi: 10.1073/pnas.82.19.6409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Todaro G. J., Fryling C., De Larco J. E. Transforming growth factors produced by certain human tumor cells: polypeptides that interact with epidermal growth factor receptors. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5258–5262. doi: 10.1073/pnas.77.9.5258. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Westermark B., Larsson E., Brunk U., Lubitz W., Mark J. Establishment of attached and non-attached cell lines from an uncommon human glioma. Int J Cancer. 1981 Sep 15;28(3):341–351. doi: 10.1002/ijc.2910280314. [DOI] [PubMed] [Google Scholar]
  34. de Tribolet N., Carrel S., Mach J. P. Brain tumor-associated antigens. Prog Exp Tumor Res. 1984;27:118–131. doi: 10.1159/000408226. [DOI] [PubMed] [Google Scholar]

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