Overexpression of gastrin-releasing peptide receptors in tumor-associated blood vessels of human ovarian neoplasms.
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 (125)I-[D-Tyr(6), beta-Ala(11), Phe(13), Nle(14)]-bombesin(6-14) and the GRP-receptor subtype-preferring (125)I-[Tyr(4)]-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.
Fleischmann
Achim
A
Institute of Pathology, University of Berne, Switzerland.
Waser
Beatrice
B
Reubi
Jean Claude
JC
D001345:Autoradiography; D001667:Binding, Competitive; D005260:Female; D006801:Humans; D009389:Neovascularization, Pathologic; D010051:Ovarian Neoplasms / Q000098:blood supply* / Q000473:pathology; D018004:Receptors, Bombesin / Q000378:metabolism*
D018004:Receptors, Bombesin