Induction of FGF receptor 2-IIIb expression and response to its ligands inepithelial ovarian cancer

Epithelial ovarian cancers (EOCs) arise in the Ovarian Surface Epithelium ( OSE). This tissue is a simple, poorly committed mesothelium which exhibits characteristics of epithelial and mesenchymal cells when grown in culture. In contrast, EOCs frequently exhibit properties of complex epithelial tissu es of the female reproductive tract, such as oviductal, endometrial and cer vical epithelia, and show induction of expression of epithelial markers suc h as E-cadherin. Fibroblast Growth Factor Receptor 2 isoform IIIb (FGF rece ptor 2-IIIb) is a spliced variant of FGF receptor 2 that binds the ligands FGF-1 and FGF-7 with high affinity, and is expressed exclusively by epithel ial cells. We have studied the expression of FGF receptor 2-IIIb and its li gands in primary cultures of normal human OSE, EOC cell lines and snap froz en tissue from EOCs. Expression of FGF receptor 2-IIIb mRNA is undetectable in normal OSE, but is expressed in 16/20 (80%) of EOCs. FGFs 1 and 7 mRNAs are expressed in normal OSE, whilst only 4/20 (20%) and 12/20 (60%) of EOC s demonstrated expression for these ligands respectively. However, FGF-7 pr otein was detected in 70% (mean level = 0.7 ng/ml) of ascitic fluids obtain ed from patients with EOC. FGFs 1 and 7 stimulate DNA synthesis in EOC cell lines that express FGF receptor 2-IIlb. Moreover, DNA synthesis in these c ell lines can be partially blocked by blocking antisera to FGFs 1 and 7. It is suggested that induction of expression of FGF receptor 2-IIIb may play a role in the development of EOCs by rendering the OSE susceptible to parac rine and/or autocrine stimulation by its requisite FGF ligands.