Bombesin-like
peptides can function as autocrine or paracrine
growth factors and stimulate the growth of various
cancers. The antagonists of
bombesin/
gastrin-releasing peptide (GRP) suppress the proliferation of diverse
tumors including
ovarian cancer by mechanisms likely mediated by
bombesin receptors. In this study, we used the reverse transcription-polymerase chain reaction (RT-PCR) method to evaluate the
mRNA expression of three
bombesin receptor subtypes:
gastrin-releasing peptide receptor (GRPR),
neuromedin B receptor (NMBR), and
bombesin receptor subtype 3 (BRS-3), in 22 specimens of human
epithelial ovarian cancer and in two human
ovarian cancer lines. Of the 22
ovarian cancer specimens analyzed, 17
tumors ( approximately 77%) expressed
mRNA for GRPR, 19 ( approximately 86%) showed NMBR
mRNA and six ( approximately 27%) revealed
BRS-3 mRNA. Thus, 14 of 22 specimens ( approximately 64%) expressed mRNAs for both GRPR and NMBR, and five ( approximately 23%) expressed all three subtypes. The expression of GRPR appeared to be greater in poorly differentiated ovarian
carcinomas. A higher incidence of
BRS-3 expression was observed in samples with
tumor Stage IV (4/4, 100%) compared with Stage III (1/17, approximately 6%).
mRNA for both GRPR and NMBR was also detected in OV-1063 and UCI-107 human
ovarian cancer xenografts, but
BRS-3 was found only in OV-1063, which originated from a metastatic
tumor. In addition, functional receptors for
bombesin/GRP were found in eight of 11
ovarian cancer specimens investigated and in both
ovarian cancer lines by receptor binding assay. Our study indicates that GRPR and NMBR are widely distributed in human ovarian
carcinomas with
BRS-3 being found in Stage IV
tumors. Some approaches based on
bombesin/GRP receptor antagonists or targeted
bombesin analogs could be considered for treatment of
ovarian cancers.