The presence of receptors for bombesin/GRP and mRNA for three receptor subtypes in human ovarian epithelial cancers.
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.
Sun
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Endocrine Polypeptide and Cancer Institute, Veterans Affairs Medical Center, 1601 Perdido Street, 70112-1262, New Orleans, LA, USA.
Schally
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AV
Halmos
G
G
D000368:Aged; D000818:Animals; D001839:Bombesin / Q000378:metabolism; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D010053:Ovary / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis*; D011869:Radioligand Assay; D018004:Receptors, Bombesin / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D018004:Receptors, Bombesin; C107120:bombesin receptor subtype 3; D001839:Bombesin