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Expression of endocrine gland-derived vascular endothelial growth factor in ovarian carcinoma
Lin Zhang1, Nuo Yang, Jose-Ramon Conejo-Garcia
1Center for Research on Reproduction and Women's Health, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
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.
Insights
Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is less abundant in ovarian cancer tissues, suggesting it may not drive tumor growth. EG-VEGF targeted therapies might benefit early-stage ovarian cancer.
Area of Science:
- Oncology
- Molecular Biology
- Angiogenesis Research
Background:
- Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is a novel angiogenic molecule identified in the human ovary.
- Its role in ovarian neoplasms and potential as a therapeutic target remain largely unexplored.
Purpose of the Study:
- To investigate the expression patterns of EG-VEGF mRNA in normal human tissues and various ovarian neoplasms.
- To evaluate the correlation between EG-VEGF expression and clinical outcomes in ovarian cancer.
- To assess the potential of EG-VEGF as a target for antiangiogenic therapy in ovarian carcinoma.
Main Methods:
- Quantitative real-time reverse transcription-PCR was employed to analyze EG-VEGF mRNA expression.
- Expression levels were compared between normal ovarian tissues, benign neoplasms, low malignant potential neoplasms, and ovarian carcinomas at different stages.
- EG-VEGF expression was also examined in ovarian cancer cell lines, cultured ovarian surface epithelial cells, peripheral blood, and tumor-infiltrating T lymphocytes.
Main Results:
- EG-VEGF mRNA was detected in all examined ovarian neoplasms, but at lower levels than in normal premenopausal ovaries.
- mRNA levels were significantly lower in late-stage compared to early-stage ovarian carcinomas.
- EG-VEGF was undetectable in epithelial ovarian cancer cell lines and ovarian surface epithelial cells, but present in peripheral blood and T lymphocytes.
- EG-VEGF mRNA levels did not correlate with clinical outcome in advanced ovarian carcinoma.
Conclusions:
- EG-VEGF expression is reduced in ovarian neoplasms compared to normal ovaries and decreases with advancing stage.
- EG-VEGF likely originates from non-epithelial components within ovarian carcinomas.
- EG-VEGF may play a limited role in angiogenesis in advanced ovarian cancer, suggesting potential utility for EG-VEGF-targeted therapies in early-stage disease.