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Expression of Insulin-like Growth Factor I, Its Binding Proteins, and Its Receptor in Ovarian Cancer¹

Division of Medical Oncology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78284 [D. Y., F. R. M., D. D. V. H.], and Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111 [T. C. H.]

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. IGF-I 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_r 24,000 species, and an M_r 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.

¹ Supported by National Cancer Institute Grant R29 CA52592 and an institional grant (IN-116 K) from the American Cancer Society (D.Y.). D. Y. is a Pew Scholar in the Biomedical Sciences.

² To whom reprint requests should be addressed, at Division of Medical Oncology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78284.

Received 4/18/91. Accepted 7/17/91.

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