Expression of endocrine gland-derived vascular endothelial growth factor in ovarian carcinoma

Lin Zhang, Nuo Yang, Jose Ramon Conejo-Garcia, Dionyssios Katsaros, Alisha Mohamed-Hadley, Stefano Fracchioli, Katia Schlienger, Alanna Toll, Bruce Levine, Stephen C. Rubin, George Coukos

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

Abstract

The first tissue-specific angiogenic molecule, endocrine gland-derived vascular endothelial growth factor (EG-VEGF), was identified recently in human ovary, raising hopes of developing tumor type-specific angiogenesis inhibitors. In the present study, we analyzed the expression of EG-VEGF mRNA in normal human tissues and ovarian neoplasms by quantitative real-time reverse transcription-PCR. EG-VEGF mRNA was expressed in all ovarian neoplasms examined. No significant difference was identified among benign, low malignant potential neoplasms or stage I ovarian cancer, all of which exhibited 2-fold lower mRNA levels compared with normal premenopausal ovaries. EG-VEGF mRNA levels further decreased in late stage compared with early stage carcinomas (P < 0.05) and were consistently lower in laser capture microdissected tumor islets compared with surrounding stroma. EG-VEGF was undetectable by reverse transcription-PCR in 17 established epithelial ovarian cancer cell lines or in cultured human ovarian surface epithelial cells, whereas it was detected in peripheral blood as well as tumor-infiltrating T lymphocytes. Finally, in contrast to VEGF, EG-VEGF mRNA levels did not correlate with clinical outcome in advanced ovarian carcinoma. These results suggest that EG-VEGF is most likely derived from nonepithelial components of ovarian carcinomas and may play a marginal role in promoting angiogenesis in advanced ovarian carcinoma. We postulate that EG-VEGF-targeted antiangiogenic therapy may prove useful in early stage but not in advanced stage ovarian carcinoma.

Original languageEnglish
Pages (from-to)264-272
Number of pages9
JournalClinical Cancer Research
Volume9
Issue number1
StatePublished - Jan 1 2003

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