Expression of endocrine gland-derived vascular endothelial growth factor in ovarian carcinoma.
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.
Zhang
Lin
L
Center for Research on Reproduction and Women's Health, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Yang
Nuo
N
Conejo-Garcia
Jose-Ramon
JR
Katsaros
Dionyssios
D
Mohamed-Hadley
Alisha
A
Fracchioli
Stefano
S
Schlienger
Katia
K
Toll
Alanna
A
Levine
Bruce
B
Rubin
Stephen C
SC
Coukos
George
G
D043925:Angiogenesis Inducing Agents / Q000096:biosynthesis*; D002277:Carcinoma / Q000378:metabolism*; D004702:Endocrine Glands / Q000378:metabolism*; D016228:Endothelial Growth Factors / Q000096:biosynthesis*; D005260:Female; D005434:Flow Cytometry; D005768:Gastrointestinal Hormones / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis*; D007834:Lasers; D008222:Lymphokines / Q000096:biosynthesis*; D008856:Microscopy, Fluorescence; D010051:Ovarian Neoplasms / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014018:Tissue Distribution; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived; D042442:Vascular Endothelial Growth Factors
D043925:Angiogenesis Inducing Agents; D016228:Endothelial Growth Factors; D005768:Gastrointestinal Hormones; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; C467610:PROK1 protein, human; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived; D042442:Vascular Endothelial Growth Factors