Affiliations: Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Berne, CH-3010 Berne, Switzerland
Note: [] Corresponding author: Jean Claude Reubi, MD, Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Berne, Murtenstrasse 31, PO Box 62, CH-3010 Berne, Switzerland. Tel.: +41 31 632 32 43; Fax: +41 31 632 89 99; E-mail: [email protected]
Abstract: Background: Peptide receptors, overexpressed in specific cancers, represent new diagnostic and therapeutic targets. In this study, receptors for the gastrin-releasing peptide (GRP), and other members of the bombesin-family of peptides, were evaluated in ovarian neoplasms. Methods: 75 primary, secondary and metastatic ovarian tumors were investigated for their bombesin-receptor subtype expression, incidence, localization and density using in vitro autoradiography on tissue sections with the universal radioligand 125I-[D-Tyr6, ß-Ala11, Phe13, Nle14]-bombesin(6-14) and the GRP-receptor subtype-preferring 125I-[Tyr4]-bombesin. Results: GRP-receptors were detected in 42/61 primary ovarian tumors; other bombesin-receptor subtypes (BB1, bb3) were rarely present (3/61). Two different tissue compartments expressed GRP-receptors: the tumoral vasculature was the predominant site of GRP-receptor expression (38/61), whereas neoplastic cells more rarely expressed GRP-receptors (14/61). GRP-receptor positive vessels were present in the various classes of ovarian tumors; generally, malignant tumors had a higher incidence of GRP-receptor positive vessels compared to their benign counterparts. The prevalence of such vessels was particularly high in ovarian carcinomas (16/19) and their metastases (5/5). The GRP-receptors were expressed in high density in the muscular vessel wall. Normal ovary (n=10) lacked GRP-receptors. Conclusions: The large amounts of GRP-receptors in ovarian tumor vessels suggest a role in tumoral vasculature and possibly angiogenesis. Further, these vessels might be targeted in vivo with bombesin analogs for diagnosis or for therapy.
