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 (PIGF), 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 PIGF, were present in all ovarian tissues examined. By in situ hybridization, neither
VEGF-C nor PIGF 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.