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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1990 Feb;87(4):1323–1327. doi: 10.1073/pnas.87.4.1323

Purification of a glycoprotein vascular endothelial cell mitogen from a rat glioma-derived cell line.

G Conn 1, D D Soderman 1, M T Schaeffer 1, M Wile 1, V B Hatcher 1, K A Thomas 1
PMCID: PMC53467  PMID: 2406719

Abstract

A growth factor that is mitogenic for vascular endothelial cells, with an ED50 of approximately 1 ng/ml, has been purified 170,000-fold to apparent homogeneity from tissue culture medium conditioned by a rat glioma-derived cell line. The pure protein is a 46-kDa dimer composed of two subunits of equivalent mass as established by comparison of migration in SDS/polyacrylamide gels with and without prior reduction. This glioma-derived growth factor is a glycoprotein and is not mitogenic for BALB/c 3T3 fibroblasts, properties that further distinguish it from other well-characterized vascular endothelial cell mitogens. In contrast to acidic and basic fibroblast growth factors and to platelet-derived endothelial cell growth factor, which have no secretory leader sequences and might only be released by leakage from damaged cells, the glycoprotein nature of this mitogen implies that it is processed through the glycosylating secretory pathway. This secretable growth factor could, therefore, be readily available in the extracellular space under normal physiological conditions in vivo to promote vascular endothelial cell proliferation associated with blood-vessel growth and maintenance.

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Selected References

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  1. Bussolino F., Wang J. M., Defilippi P., Turrini F., Sanavio F., Edgell C. J., Aglietta M., Arese P., Mantovani A. Granulocyte- and granulocyte-macrophage-colony stimulating factors induce human endothelial cells to migrate and proliferate. Nature. 1989 Feb 2;337(6206):471–473. doi: 10.1038/337471a0. [DOI] [PubMed] [Google Scholar]
  2. Böhlen P., Baird A., Esch F., Ling N., Gospodarowicz D. Isolation and partial molecular characterization of pituitary fibroblast growth factor. Proc Natl Acad Sci U S A. 1984 Sep;81(17):5364–5368. doi: 10.1073/pnas.81.17.5364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Damon D. H., D'Amore P. A., Wagner J. A. Sulfated glycosaminoglycans modify growth factor-induced neurite outgrowth in PC12 cells. J Cell Physiol. 1988 May;135(2):293–300. doi: 10.1002/jcp.1041350217. [DOI] [PubMed] [Google Scholar]
  4. Delli Bovi P., Curatola A. M., Kern F. G., Greco A., Ittmann M., Basilico C. An oncogene isolated by transfection of Kaposi's sarcoma DNA encodes a growth factor that is a member of the FGF family. Cell. 1987 Aug 28;50(5):729–737. doi: 10.1016/0092-8674(87)90331-x. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Ferrara N., Henzel W. J. Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochem Biophys Res Commun. 1989 Jun 15;161(2):851–858. doi: 10.1016/0006-291x(89)92678-8. [DOI] [PubMed] [Google Scholar]
  7. Gimenez-Gallego G., Conn G., Hatcher V. B., Thomas K. A. The complete amino acid sequence of human brain-derived acidic fibroblast growth factor. Biochem Biophys Res Commun. 1986 Jul 31;138(2):611–617. doi: 10.1016/s0006-291x(86)80540-x. [DOI] [PubMed] [Google Scholar]
  8. Gordon P. B., Sussman I. I., Hatcher V. B. Long-term culture of human endothelial cells. In Vitro. 1983 Sep;19(9):661–671. doi: 10.1007/BF02628957. [DOI] [PubMed] [Google Scholar]
  9. Ishikawa F., Miyazono K., Hellman U., Drexler H., Wernstedt C., Hagiwara K., Usuki K., Takaku F., Risau W., Heldin C. H. Identification of angiogenic activity and the cloning and expression of platelet-derived endothelial cell growth factor. Nature. 1989 Apr 13;338(6216):557–562. doi: 10.1038/338557a0. [DOI] [PubMed] [Google Scholar]
  10. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  11. Lemmon S. K., Bradshaw R. A. Purification and partial characterization of bovine pituitary fibroblast growth factor. J Cell Biochem. 1983;21(3):195–208. doi: 10.1002/jcb.240210302. [DOI] [PubMed] [Google Scholar]
  12. Marics I., Adelaide J., Raybaud F., Mattei M. G., Coulier F., Planche J., de Lapeyriere O., Birnbaum D. Characterization of the HST-related FGF.6 gene, a new member of the fibroblast growth factor gene family. Oncogene. 1989 Mar;4(3):335–340. [PubMed] [Google Scholar]
  13. Miyazono K., Okabe T., Urabe A., Takaku F., Heldin C. H. Purification and properties of an endothelial cell growth factor from human platelets. J Biol Chem. 1987 Mar 25;262(9):4098–4103. [PubMed] [Google Scholar]
  14. Smith R., Peters G., Dickson C. Multiple RNAs expressed from the int-2 gene in mouse embryonal carcinoma cell lines encode a protein with homology to fibroblast growth factors. EMBO J. 1988 Apr;7(4):1013–1022. doi: 10.1002/j.1460-2075.1988.tb02908.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Thomas K. A., Rios-Candelore M., Fitzpatrick S. Purification and characterization of acidic fibroblast growth factor from bovine brain. Proc Natl Acad Sci U S A. 1984 Jan;81(2):357–361. doi: 10.1073/pnas.81.2.357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. Yoshida T., Miyagawa K., Odagiri H., Sakamoto H., Little P. F., Terada M., Sugimura T. Genomic sequence of hst, a transforming gene encoding a protein homologous to fibroblast growth factors and the int-2-encoded protein. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7305–7309. doi: 10.1073/pnas.84.20.7305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Zhan X., Bates B., Hu X. G., Goldfarb M. The human FGF-5 oncogene encodes a novel protein related to fibroblast growth factors. Mol Cell Biol. 1988 Aug;8(8):3487–3495. doi: 10.1128/mcb.8.8.3487. [DOI] [PMC free article] [PubMed] [Google Scholar]

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