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Vascular endothelial growth
factor (VEGF) is an angiogenic factor secreted by various tumors, including
epithelial tumors of the ovary, and is involved in tumor progression and
maintenance. The significance and function of other members of the VEGF
family in the ovary has not yet been elucidated. In the present study, we
have defined the expression of mRNA encoding VEGF-B, VEGF-C, and placenta
growth factor (PlGF), compared with that of VEGF mRNA, in normal ovary and
a range of ovarian epithelial tumors. Analysis by reverse transcription-PCR
indicated that mRNA encoding VEGF (isoforms 121 and 165), VEGF-B (isoforms
167 and 186), and VEGF-C, but not PlGF, were present in all ovarian tissues
examined. By in situ hybridization, neither VEGF-C nor PlGF transcripts
were detected in any of the samples. The expression pattern of VEGF-B mRNA
was generally similar to that of VEGF mRNA, in that transcripts were readily
detected in the epithelial cells of all histologic types of ovarian carcinoma,
but could not be detected in normal or benign tumor epithelium. Specific
differences in the expression of the two genes were noted in areas of tumor
necrosis, in which the expression of VEGF mRNA, but not VEGF-B mRNA, was
further enhanced, and in a sample in which VEGF-B mRNA was strongly expressed
in tumor-associated macrophages that did not hybridize with the riboprobe
to VEGF mRNA. These results imply that a second member of the VEGF family,
VEGF-B, may play a significant role in the angiogenesis, progression, and
maintenance of ovarian carcinomas. |
