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. 1988 Sep 1;107(3):1199–1205. doi: 10.1083/jcb.107.3.1199

Autocrine activities of basic fibroblast growth factor: regulation of endothelial cell movement, plasminogen activator synthesis, and DNA synthesis

PMCID: PMC2115297  PMID: 3417781

Abstract

We have found that the spontaneous migration of bovine aortic endothelial cells from the edge of a denuded area in a confluent monolayer is dependent upon the release of endogenous basic fibroblast growth factor (bFGF). Cell movement is blocked by purified polyclonal rabbit IgG to bFGF as well as affinity purified anti-bFGF IgG and anti- bFGF F(ab')2 fragments. The inhibitory effect of the immunoglobulins is dependent upon antibody concentration, is reversible, is overcome by the addition of recombinant bFGF, and is removed by affinity chromatography of the antiserum through a column of bFGF-Sepharose. Cell movement is also reversibly inhibited by the addition of protamine sulfate and suramin; two agents reported to block bFGF binding to its receptor. The addition of recombinant bFGF to wounded monolayers accelerates the movement of cells into the denuded area. Transforming growth factor beta which has been shown to antagonize several other effects of bFGF also inhibits cell movement. The anti-bFGF IgG prevents the movement of bovine capillary endothelial cells, BHK-21, NIH 3T3, and human skin fibroblasts into a denuded area. Antibodies to bFGF, as well as suramin and protamine sulfate also suppress the basal levels of plasminogen activator and DNA synthesis in bovine aortic endothelial cells.

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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. Abraham J. A., Whang J. L., Tumolo A., Mergia A., Friedman J., Gospodarowicz D., Fiddes J. C. Human basic fibroblast growth factor: nucleotide sequence and genomic organization. EMBO J. 1986 Oct;5(10):2523–2528. doi: 10.1002/j.1460-2075.1986.tb04530.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baird A., Durkin T. Inhibition of endothelial cell proliferation by type beta-transforming growth factor: interactions with acidic and basic fibroblast growth factors. Biochem Biophys Res Commun. 1986 Jul 16;138(1):476–482. doi: 10.1016/0006-291x(86)90305-0. [DOI] [PubMed] [Google Scholar]
  4. Baird A., Schubert D., Ling N., Guillemin R. Receptor- and heparin-binding domains of basic fibroblast growth factor. Proc Natl Acad Sci U S A. 1988 Apr;85(7):2324–2328. doi: 10.1073/pnas.85.7.2324. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bürk R. R. A factor from a transformed cell line that affects cell migration. Proc Natl Acad Sci U S A. 1973 Feb;70(2):369–372. doi: 10.1073/pnas.70.2.369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Coffey R. J., Jr, Leof E. B., Shipley G. D., Moses H. L. Suramin inhibition of growth factor receptor binding and mitogenicity in AKR-2B cells. J Cell Physiol. 1987 Jul;132(1):143–148. doi: 10.1002/jcp.1041320120. [DOI] [PubMed] [Google Scholar]
  7. Fràter-Schröder M., Müller G., Birchmeier W., Böhlen P. Transforming growth factor-beta inhibits endothelial cell proliferation. Biochem Biophys Res Commun. 1986 May 29;137(1):295–302. doi: 10.1016/0006-291x(86)91209-x. [DOI] [PubMed] [Google Scholar]
  8. Gospodarowicz D., Moran J., Braun D., Birdwell C. Clonal growth of bovine vascular endothelial cells: fibroblast growth factor as a survival agent. Proc Natl Acad Sci U S A. 1976 Nov;73(11):4120–4124. doi: 10.1073/pnas.73.11.4120. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gospodarowicz D., Neufeld G., Schweigerer L. Fibroblast growth factor: structural and biological properties. J Cell Physiol Suppl. 1987;Suppl 5:15–26. doi: 10.1002/jcp.1041330405. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Hatten M. E., Lynch M., Rydel R. E., Sanchez J., Joseph-Silverstein J., Moscatelli D., Rifkin D. B. In vitro neurite extension by granule neurons is dependent upon astroglial-derived fibroblast growth factor. Dev Biol. 1988 Feb;125(2):280–289. doi: 10.1016/0012-1606(88)90211-4. [DOI] [PubMed] [Google Scholar]
  12. Heimark R. L., Twardzik D. R., Schwartz S. M. Inhibition of endothelial regeneration by type-beta transforming growth factor from platelets. Science. 1986 Sep 5;233(4768):1078–1080. doi: 10.1126/science.3461562. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Kurokawa T., Sasada R., Iwane M., Igarashi K. Cloning and expression of cDNA encoding human basic fibroblast growth factor. FEBS Lett. 1987 Mar 9;213(1):189–194. doi: 10.1016/0014-5793(87)81489-8. [DOI] [PubMed] [Google Scholar]
  15. Morioka S., Lazarus G. S., Baird J. L., Jensen P. J. Migrating keratinocytes express urokinase-type plasminogen activator. J Invest Dermatol. 1987 Apr;88(4):418–423. doi: 10.1111/1523-1747.ep12469754. [DOI] [PubMed] [Google Scholar]
  16. Morrison R. S., Sharma A., de Vellis J., Bradshaw R. A. Basic fibroblast growth factor supports the survival of cerebral cortical neurons in primary culture. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7537–7541. doi: 10.1073/pnas.83.19.7537. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Moscatelli D. High and low affinity binding sites for basic fibroblast growth factor on cultured cells: absence of a role for low affinity binding in the stimulation of plasminogen activator production by bovine capillary endothelial cells. J Cell Physiol. 1987 Apr;131(1):123–130. doi: 10.1002/jcp.1041310118. [DOI] [PubMed] [Google Scholar]
  18. Moscatelli D., Presta M., Joseph-Silverstein J., Rifkin D. B. Both normal and tumor cells produce basic fibroblast growth factor. J Cell Physiol. 1986 Nov;129(2):273–276. doi: 10.1002/jcp.1041290220. [DOI] [PubMed] [Google Scholar]
  19. Moscatelli D., Presta M., Rifkin D. B. Purification of a factor from human placenta that stimulates capillary endothelial cell protease production, DNA synthesis, and migration. Proc Natl Acad Sci U S A. 1986 Apr;83(7):2091–2095. doi: 10.1073/pnas.83.7.2091. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Neufeld G., Ferrara N., Schweigerer L., Mitchell R., Gospodarowicz D. Bovine granulosa cells produce basic fibroblast growth factor. Endocrinology. 1987 Aug;121(2):597–603. doi: 10.1210/endo-121-2-597. [DOI] [PubMed] [Google Scholar]
  21. Neufeld G., Gospodarowicz D. Protamine sulfate inhibits mitogenic activities of the extracellular matrix and fibroblast growth factor, but potentiates that of epidermal growth factor. J Cell Physiol. 1987 Aug;132(2):287–294. doi: 10.1002/jcp.1041320213. [DOI] [PubMed] [Google Scholar]
  22. Ossowski L., Quigley J. P., Kellerman G. M., Reich E. Fibrinolysis associated with oncogenic transformation. Requirement of plasminogen for correlated changes in cellular morphology, colony formation in agar, and cell migration. J Exp Med. 1973 Nov 1;138(5):1056–1064. doi: 10.1084/jem.138.5.1056. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Pepper M. S., Vassalli J. D., Montesano R., Orci L. Urokinase-type plasminogen activator is induced in migrating capillary endothelial cells. J Cell Biol. 1987 Dec;105(6 Pt 1):2535–2541. doi: 10.1083/jcb.105.6.2535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Presta M., Moscatelli D., Joseph-Silverstein J., Rifkin D. B. Purification from a human hepatoma cell line of a basic fibroblast growth factor-like molecule that stimulates capillary endothelial cell plasminogen activator production, DNA synthesis, and migration. Mol Cell Biol. 1986 Nov;6(11):4060–4066. doi: 10.1128/mcb.6.11.4060. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Rogelj S., Weinberg R. A., Fanning P., Klagsbrun M. Basic fibroblast growth factor fused to a signal peptide transforms cells. Nature. 1988 Jan 14;331(6152):173–175. doi: 10.1038/331173a0. [DOI] [PubMed] [Google Scholar]
  26. Saksela O., Moscatelli D., Rifkin D. B. The opposing effects of basic fibroblast growth factor and transforming growth factor beta on the regulation of plasminogen activator activity in capillary endothelial cells. J Cell Biol. 1987 Aug;105(2):957–963. doi: 10.1083/jcb.105.2.957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Sasada R., Kurokawa T., Iwane M., Igarashi K. Transformation of mouse BALB/c 3T3 cells with human basic fibroblast growth factor cDNA. Mol Cell Biol. 1988 Feb;8(2):588–594. doi: 10.1128/mcb.8.2.588. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Schweigerer L., Malerstein B., Neufeld G., Gospodarowicz D. Basic fibroblast growth factor is synthesized in cultured retinal pigment epithelial cells. Biochem Biophys Res Commun. 1987 Mar 30;143(3):934–940. doi: 10.1016/0006-291x(87)90340-8. [DOI] [PubMed] [Google Scholar]
  29. Schweigerer L., Neufeld G., Friedman J., Abraham J. A., Fiddes J. C., Gospodarowicz D. Basic fibroblast growth factor: production and growth stimulation in cultured adrenal cortex cells. Endocrinology. 1987 Feb;120(2):796–800. doi: 10.1210/endo-120-2-796. [DOI] [PubMed] [Google Scholar]
  30. Schweigerer L., Neufeld G., Friedman J., Abraham J. A., Fiddes J. C., Gospodarowicz D. Capillary endothelial cells express basic fibroblast growth factor, a mitogen that promotes their own growth. Nature. 1987 Jan 15;325(6101):257–259. doi: 10.1038/325257a0. [DOI] [PubMed] [Google Scholar]
  31. Sommer A., Brewer M. T., Thompson R. C., Moscatelli D., Presta M., Rifkin D. B. A form of human basic fibroblast growth factor with an extended amino terminus. Biochem Biophys Res Commun. 1987 Apr 29;144(2):543–550. doi: 10.1016/s0006-291x(87)80001-3. [DOI] [PubMed] [Google Scholar]
  32. Stoker M., Piggott D. Shaking 3T3 cells: further studies on diffusion boundary effects. Cell. 1974 Nov;3(3):207–215. doi: 10.1016/0092-8674(74)90133-0. [DOI] [PubMed] [Google Scholar]
  33. Vlodavsky I., Folkman J., Sullivan R., Fridman R., Ishai-Michaeli R., Sasse J., Klagsbrun M. Endothelial cell-derived basic fibroblast growth factor: synthesis and deposition into subendothelial extracellular matrix. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2292–2296. doi: 10.1073/pnas.84.8.2292. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Vlodavsky I., Fridman R., Sullivan R., Sasse J., Klagsbrun M. Aortic endothelial cells synthesize basic fibroblast growth factor which remains cell associated and platelet-derived growth factor-like protein which is secreted. J Cell Physiol. 1987 Jun;131(3):402–408. doi: 10.1002/jcp.1041310312. [DOI] [PubMed] [Google Scholar]
  35. Walicke P., Cowan W. M., Ueno N., Baird A., Guillemin R. Fibroblast growth factor promotes survival of dissociated hippocampal neurons and enhances neurite extension. Proc Natl Acad Sci U S A. 1986 May;83(9):3012–3016. doi: 10.1073/pnas.83.9.3012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. van Mourik J. A., Lawrence D. A., Loskutoff D. J. Purification of an inhibitor of plasminogen activator (antiactivator) synthesized by endothelial cells. J Biol Chem. 1984 Dec 10;259(23):14914–14921. [PubMed] [Google Scholar]

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