Expression of Insulin-like Growth Factor I, Its Binding Proteins, and Its Receptor in Ovarian Cancer

Insulin-like growth factor (IGF) I is a polypeptide hormone important in normal growth and development. Although IGF-I is a mitogen for many cancer cell lines, previous work has suggested that autocrine production of IGF-I is uncommon in cancers of epithelial origin. In this study, expression of IGF-I, its binding proteins, and its receptor were examined in ovarian cancer cell lines and tissues. Of 10 ovarian cancer cell lines, 3 (OVCAR-3, OVCAR-7, and PEO4) expressed IGF-I mRNA. RNase protection assays using probes derived from IGF-IA, IGF-IB, and alternate exon 1 IGF-I complementary DNAs demonstrated that these cells contained a predominant IGF-I transcript with an alternate first exon. RNA extracted from primary and metastatic ovarian cancer tissues also expressed IGF-I mRNAs (7 of 7) with the alternate first exon. IGFI protein was detected in OVCAR-3-conditioned media; this activity was secreted in conjunction with several IGF-binding proteins (IGFBPs). IGFBP-2, IGFBP-3, an M, 24,000 species, and an M, 30,000 species could also be demonstrated in OVCAR-3. Type I IGF receptor mRNA was found in all 10 of the ovarian cancer cell lines and all 7 of the primary or metastatic ovarian cancer tissues. IGF-I was a mitogen for OVCAR- 3, demonstrating the presence of a functional type I IGF receptor. These data show that all the necessary components for an IGF-I-mediated autocrine loop are expressed by ovarian cancer cells.