BASIC FIBROBLAST GROWTH-FACTOR AND RECEPTOR EXPRESSION IN HUMAN OVARIAN-CANCER

Basic fibroblast growth factor (bFGF) and other members of the FGF fam ily share several biological properties that have the potential to med iate neoplastic cell growth. To test the hypothesis that bFGF may play a role in human ovarian cancer cell growth, three ovarian cancer cell lines, A90, A121(P), and A121(A), were investigated for their ability to respond to bFGF as a mitogen, to express endogenous bFGF protein o r message for FGF proteins, and to exhibit FGF receptor or its message . Addition of bFGF to cultures of all three cell lines maintained in c hemically defined media resulted in a statistically significant increa se in cell number. Cell extracts from A90, A121(P), and A121(A) contai ned an immunoreactive protein that comigrated with hr-bFGF by Western blot analysis. Several bands of higher molecular weight were also note d. Immunohistochemical staining for bFGF demonstrated a cytoplasmic di stribution of bFGF in the three cell lines. Both high- and low-affinit y binding sites for human recombinant bFGF (hr-bFGF) were expressed by all three lines. High-affinity sites varied from 2700 sites per cell (K-d = 29 pM) to 13,500 sites per cell (K-d = 71 pM) Ah three cell lin es were screened for mRNA expression for seven FGF proteins and four F GF receptors. In all three lines, mRNA for FGF2 (bFGF) was detected by PCR analysis, and in two lines, mRNA for FGF1 (aFGF) and FGF5 were al so found. The FGFR1 receptor subtype (flg) was common to all of the ce ll. lines. Finally, suramin inhibited proliferation of A90 and A121 (P and A) with IC50's of 60 and 210 mu g/ml, respectively. This is consi stent with the A90 cell line having higher levels of endogenous bFGF a nd flg and therefore being more responsive to suramin inhibition than the A121 cell line, The results indicate that these ovarian cancer cel l lines can produce bFGF as well as other members of the FGF family of genes and have the ability to respond to bFGF. (C) 1994 Academic Pres s, Inc.