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. 1986 Apr;83(7):2091–2095. doi: 10.1073/pnas.83.7.2091

Purification of a factor from human placenta that stimulates capillary endothelial cell protease production, DNA synthesis, and migration.

D Moscatelli, M Presta, D B Rifkin
PMCID: PMC323236  PMID: 3008151

Abstract

A protein that stimulates the production of plasminogen activator and latent collagenase in cultured bovine capillary endothelial cells has been purified 10(6)-fold from term human placenta by using a combination of heparin affinity chromatography, ion-exchange chromatography, and gel chromatography. The purified molecule has a molecular weight of 18,700 as determined by NaDodSO4/PAGE under both reducing and nonreducing conditions. The purified molecule stimulates the production of plasminogen activator and latent collagenase in a dose-dependent manner between 0.1 and 10 ng of protein/ml. The purified protein also stimulates DNA synthesis and chemotaxis in capillary endothelial cells in the same concentration range. Thus, this molecule has all of the properties predicted for an angiogenic factor.

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Selected References

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

  1. Burgos H. Angiogenic and growth factors in human amnio-chorion and placenta. Eur J Clin Invest. 1983 Aug;13(4):289–296. doi: 10.1111/j.1365-2362.1983.tb00103.x. [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. Castellot J. J., Jr, Karnovsky M. J., Spiegelman B. M. Differentiation-dependent stimulation of neovascularization and endothelial cell chemotaxis by 3T3 adipocytes. Proc Natl Acad Sci U S A. 1982 Sep;79(18):5597–5601. doi: 10.1073/pnas.79.18.5597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Conn G., Hatcher V. B. The isolation and purification of two anionic endothelial cell growth factors from human brain. Biochem Biophys Res Commun. 1984 Oct 15;124(1):262–268. doi: 10.1016/0006-291x(84)90946-x. [DOI] [PubMed] [Google Scholar]
  5. D'Amore P. A., Glaser B. M., Brunson S. K., Fenselau A. H. Angiogenic activity from bovine retina: partial purification and characterization. Proc Natl Acad Sci U S A. 1981 May;78(5):3068–3072. doi: 10.1073/pnas.78.5.3068. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. D'Amore P. A., Klagsbrun M. Endothelial cell mitogens derived from retina and hypothalamus: biochemical and biological similarities. J Cell Biol. 1984 Oct;99(4 Pt 1):1545–1549. doi: 10.1083/jcb.99.4.1545. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Folkman J., Cotran R. Relation of vascular proliferation to tumor growth. Int Rev Exp Pathol. 1976;16:207–248. [PubMed] [Google Scholar]
  9. Folkman J., Haudenschild C. C., Zetter B. R. Long-term culture of capillary endothelial cells. Proc Natl Acad Sci U S A. 1979 Oct;76(10):5217–5221. doi: 10.1073/pnas.76.10.5217. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gospodarowicz D., Cheng J., Lui G. M., Baird A., Böhlent P. Isolation of brain fibroblast growth factor by heparin-Sepharose affinity chromatography: identity with pituitary fibroblast growth factor. Proc Natl Acad Sci U S A. 1984 Nov;81(22):6963–6967. doi: 10.1073/pnas.81.22.6963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gross J. L., Moscatelli D., Jaffe E. A., Rifkin D. B. Plasminogen activator and collagenase production by cultured capillary endothelial cells. J Cell Biol. 1982 Dec;95(3):974–981. doi: 10.1083/jcb.95.3.974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gross J. L., Moscatelli D., Rifkin D. B. Increased capillary endothelial cell protease activity in response to angiogenic stimuli in vitro. Proc Natl Acad Sci U S A. 1983 May;80(9):2623–2627. doi: 10.1073/pnas.80.9.2623. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Grotendorst G. R., Seppä H. E., Kleinman H. K., Martin G. R. Attachment of smooth muscle cells to collagen and their migration toward platelet-derived growth factor. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3669–3672. doi: 10.1073/pnas.78.6.3669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. Lobb R. R., Fett J. W. Purification of two distinct growth factors from bovine neural tissue by heparin affinity chromatography. Biochemistry. 1984 Dec 18;23(26):6295–6299. doi: 10.1021/bi00321a001. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Moscatelli D., Jaffe E., Rifkin D. B. Tetradecanoyl phorbol acetate stimulates latent collagenase production by cultured human endothelial cells. Cell. 1980 Jun;20(2):343–351. doi: 10.1016/0092-8674(80)90620-0. [DOI] [PubMed] [Google Scholar]
  18. Mullins D. E., Rifkin D. B. Stimulation of motility in cultured bovine capillary endothelial cells by angiogenic preparations. J Cell Physiol. 1984 May;119(2):247–254. doi: 10.1002/jcp.1041190216. [DOI] [PubMed] [Google Scholar]
  19. Presta M., Mignatti P., Mullins D. E., Moscatelli D. A. Human placental tissue stimulates bovine capillary endothelial cell growth, migration and protease production. Biosci Rep. 1985 Sep;5(9):783–790. doi: 10.1007/BF01119877. [DOI] [PubMed] [Google Scholar]
  20. Schor A. M., Schor S. L., Weiss J. B., Brown R. A., Kumar S., Phillips P. Stimulation by a low-molecular-weight angiogenic factor of capillary endothelial cells in culture. Br J Cancer. 1980 May;41(5):790–799. doi: 10.1038/bjc.1980.143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. Terranova V. P., DiFlorio R., Lyall R. M., Hic S., Friesel R., Maciag T. Human endothelial cells are chemotactic to endothelial cell growth factor and heparin. J Cell Biol. 1985 Dec;101(6):2330–2334. doi: 10.1083/jcb.101.6.2330. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. Wray W., Boulikas T., Wray V. P., Hancock R. Silver staining of proteins in polyacrylamide gels. Anal Biochem. 1981 Nov 15;118(1):197–203. doi: 10.1016/0003-2697(81)90179-2. [DOI] [PubMed] [Google Scholar]
  25. Zetter B. R. Migration of capillary endothelial cells is stimulated by tumour-derived factors. Nature. 1980 May 1;285(5759):41–43. doi: 10.1038/285041a0. [DOI] [PubMed] [Google Scholar]

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