Ligands to FGF receptor 2-IIIb induce proliferation, motility, protection from cell death and cytoskeletal rearrangements in epithelial ovarian cancer cell lines.
Epithelial ovarian cancer (EOC) is the most common and lethal form of gynecological malignancy. These cancers are thought to be derived from the ovarian surface epithelium (OSE). We have previously reported that the epithelial-specific FGF receptor 2 splice variant IIIb is not expressed in normal OSE, but is expressed in approximately 80% of EOCs. We have examined the phenotypic effects of ligands to FGF receptor 2-IIIb, namely FGFs 1,7 and 10, on a panel of EOC cell lines. We show that these ligands increase cell viability, induce DNA synthesis, motility and chemotaxis and protect from spontaneous cell death when EOC cells are maintained in serum free medium. A blocking antiserum to FGF-7 reduces viability of 41-M EOC cells, and abrogates the ability of ascitic fluid containing FGF-7 to induce DNA synthesis in these cells. Finally, we show that FGF-7 can induce a reorganization of the actin cytoskeleton in SK-OV-3 ovarian cancer cells. It is suggested that ligands to FGF receptor 2-IIIb affect a range of phenotypes important in the neoplastic growth of EOCs.
Steele
Islay A
IA
Northern Institute for Cancer Research and School of Surgical and Reproductive Sciences, Faculty of Medical Sciences, University of Newcastle, Newcastle-upon-Tyne, UK.
Edmondson
Richard J
RJ
Leung
Hing Y
HY
Davies
Barry R
BR
D000199:Actins / Q000502:physiology; D016923:Cell Death; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D002633:Chemotaxis; D016895:Culture Media, Serum-Free; D003599:Cytoskeleton / Q000502:physiology*; D004261:DNA Replication; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology*; D005260:Female; D016220:Fibroblast Growth Factor 1 / Q000378:metabolism; D051526:Fibroblast Growth Factor 10 / Q000378:metabolism; D051523:Fibroblast Growth Factor 7 / Q000378:metabolism; D006801:Humans; D008024:Ligands; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D010053:Ovary / Q000378:metabolism / Q000473:pathology*; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000378:metabolism*
D000199:Actins; D016895:Culture Media, Serum-Free; D051526:Fibroblast Growth Factor 10; D008024:Ligands; D016220:Fibroblast Growth Factor 1; D051523:Fibroblast Growth Factor 7; D051497:Receptor, Fibroblast Growth Factor, Type 2; C065104:keratinocyte growth factor receptor