Basic fibroblast growth factor is an extracellular matrix component required for supporting the proliferation of vascular endothelial cells and the differentiation of PC12 cells.
Vascular endothelial cells (ECs) seeded sparsely on extracellular matrix (ECM) will proliferate in the absence of exogenous basic fibroblast growth factor (bFGF). This ECM will also stimulate neurite outgrowth in PC12 cells in the absence of exogenous growth factors. We have previously shown that bFGF is found in subendothelial ECM (Vlodavsky, I., J. Folkman, R. Sullivan, R. Fridman, R. Ishai-Michaeli, J. Sasse, and M. Klagsburn. 1987. Proc. Natl. Acad. Sci. USA. 84:2292-2296) and in basement membranes (Folkman, J., M. Klagsburn, J. Sasse, M. Wadzinski, D. Ingber, and I. Vlodavsky. 1988. Am. J. Pathol. 130:393-400). The actual requirement of ECM-associated bFGF for the growth of ECs and differentiation of PC12 cells was shown in two ways. First, polyclonal anti-bFGF antibodies added to subendothelial ECM inhibited both EC proliferation and PC12 neurite outgrowth. Secondly, PF-HR-9 cells, which do not synthesize bFGF and which produce an ECM not permissive for EC proliferation and PC12 neurite outgrowth, were transfected with bFGF cDNA. PF-HR-9 cells transfected with bFGF, but not with the dominant selectable marker SV2-neomycin, were found to express bFGF and to produce an ECM which did support both EC proliferation and PC12 differentiation. The ECM-mediated stimulatory effects were inhibited by anti-bFGF antibodies but not by anti-nerve growth factor antibodies or nonimmune rabbit IgG. These results indicate that bFGF associated with ECM is a required ECM component for ECM-mediated cell proliferation and differentiation.
Department of Surgery, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
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Rogelj
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Klagsbrun
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Atzmon
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Kurokawa
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Haimovitz
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Fuks
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Vlodavsky
D000310:Adrenal Gland Neoplasms / Q000503:physiopathology; D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000378:metabolism; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004730:Endothelium, Vascular / Q000166:cytology*; D005109:Extracellular Matrix / Q000032:analysis*; D005346:Fibroblast Growth Factors / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation; D009474:Neurons / Q000166:cytology*; D010673:Pheochromocytoma / Q000503:physiopathology; D051381:Rats; D014162:Transfection; D014407:Tumor Cells, Cultured
D000906:Antibodies; D005346:Fibroblast Growth Factors