Expression of Endocrine Gland-derived Vascular Endothelial Growth Factor in Ovarian Carcinoma

• Published in: Clinical cancer research Vol. 9; no. 1; pp. 264 - 272
• Main Authors: LIN ZHANG, NUO YANG, COUKOS, George, CONEJO-GARCIA, Jose-Ramon, KATSAROS, Dionyssios, MOHAMED-HADLEY, Alisha, FRACCHIOLI, Stefano, SCHLIENGER, Katia, TOLL, Alanna, LEVINE, Bruce, RUBIN, Stephen C
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01-01-2003
• Subjects: Angiogenesis Inducing Agents - biosynthesis; Biological and medical sciences; Carcinoma - metabolism; Endocrine Glands - metabolism; Endothelial Growth Factors - biosynthesis; Female; Female genital diseases; Flow Cytometry; Gastrointestinal Hormones - biosynthesis; Gynecology. Andrology. Obstetrics; Humans; Immunohistochemistry; Intercellular Signaling Peptides and Proteins - biosynthesis; Lasers; Lymphokines - biosynthesis; Medical sciences; Microscopy, Fluorescence; Ovarian Neoplasms - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Time Factors; Tissue Distribution; Treatment Outcome; Tumor Cells, Cultured; Tumors; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor, Endocrine-Gland-Derived; Vascular Endothelial Growth Factors; Human; Carcinoma; Endocrine gland; Angiogenic factor; Malignant tumor; Gene expression; Female genital diseases; Ovarian diseases; Angiogenesis; Ovary; Vascular endothelium growth factor; Female; Neovascularization
• ISSN: 1078-0432; 1557-3265

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.