Our specific aims are: 1) To further characterize brain and pituitary fibroblast growth factors (FGF) already purified by FPLC, by determining their primary structure. The relationship between brain and pituitary FGF will also be determined using monoclonal antibodies developed against both molecules. Their relationship with the endothelial cell growth factor (ECGF) will be determined. 2) The interaction of bovine brain and pituitary FGF with cultured endothelial cells originating from various vascular territories and species will be determined and the FGF receptors characterized. 3) The effect in vitro of FGF on endothelial cell migration, as well as its possible role as a chemotactic agent in vitro will be determined. 4) Finally, using monoclonal antibodies agaist FGF, its distribution in various tissues, neoplasms, or cultured cells known to contain angiogenic factors in vivo will be eq. determined. The angiogenic activity of FGF in three different in vivo models (rabbit cornea, Hamster pouch, and chick chorioallantoid membrane) will be analyzed as well as the ability of FGF antibodies to block such activity in vivo. The factor(s) in basement membranes (BM) which mimics the effect of FGF will be determined. The effect of FGF on the synthesis and integration of such factors in the BM synthesized by cultured vascular endothelial cells will be analyzed. The effect of both BM and FGF on the maintenance and turnover of the transferrin receptor which is required for endothelial cells to divide, and which in vivo (erythropoietic system), or in organ culture (metanephric mesenchyme), has been shown to be inducible and to correlate with the appearance of specific BM components will be analyzed.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL020197-11
Application #
3336076
Study Section
Pathology A Study Section (PTHA)
Project Start
1976-12-01
Project End
1987-11-30
Budget Start
1986-12-01
Budget End
1987-11-30
Support Year
11
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Gospodarowicz, D; Abraham, J A; Schilling, J (1989) Isolation and characterization of a vascular endothelial cell mitogen produced by pituitary-derived folliculo stellate cells. Proc Natl Acad Sci U S A 86:7311-5
Schweigerer, L; Ferrara, N; Haaparanta, T et al. (1988) Basic fibroblast growth factor: expression in cultured cells derived from corneal endothelium and lens epithelium. Exp Eye Res 46:71-80
Gospodarowicz, D; Ferrara, N; Haaparanta, T et al. (1988) Basic fibroblast growth factor: expression in cultured bovine vascular smooth muscle cells. Eur J Cell Biol 46:144-51
Neufeld, G; Gospodarowicz, D (1988) Identification of the fibroblast growth factor receptor in human vascular endothelial cells. J Cell Physiol 136:537-42
Adashi, E Y; Resnick, C E; Croft, C S et al. (1988) Basic fibroblast growth factor as a regulator of ovarian granulosa cell differentiation: a novel non-mitogenic role. Mol Cell Endocrinol 55:7-14
Neufeld, G; Gospodarowicz, D (1987) Protamine sulfate inhibits mitogenic activities of the extracellular matrix and fibroblast growth factor, but potentiates that of epidermal growth factor. J Cell Physiol 132:287-94
Schweigerer, L; Malerstein, B; Neufeld, G et al. (1987) Basic fibroblast growth factor is synthesized in cultured retinal pigment epithelial cells. Biochem Biophys Res Commun 143:934-40
Schweigerer, L; Neufeld, G; Gospodarowicz, D (1987) Basic fibroblast growth factor as a growth inhibitor for cultured human tumor cells. J Clin Invest 80:1516-20
Schweigerer, L; Neufeld, G; Gospodarowicz, D (1987) Basic fibroblast growth factor is present in cultured human retinoblastoma cells. Invest Ophthalmol Vis Sci 28:1838-43
Massoglia, S L; Kenney, J S; Gospodarowicz, D J (1987) Characterization of murine monoclonal antibodies directed against basic fibroblast growth factor. J Cell Physiol 132:531-7

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