ISPO

Published in Cancer Detection and Prevention 1997; 21(1):62-71.

The Somatostatin Receptor Subtype 2 is Expressed in Normal and Tumoral Human Tissues

Gregoire Prevost PhD, EDR1, Robert Benamouzig MD2, Nathalie Veber PhD1, Anne Fajac MD3, Roger Tatoud PhD4, Armelle Degeorges PhD4, Peter Eden PhD5

1Institut d'Oncologie Cellulaire et Moleculaire Humaine, BPBS, Bobigny, France; 2Gastroenterologie, Hopital Avicenne, Bobigny, France; 3Institut G. Roussy, Villejuif, France; 4Hopital Saint Louis, Paris, France; and 5Biomeasure Incorporated, Milford, MA

Address all correspondence and reprint requests to: Gregoire Prevost, PhD, EDR, Institut d'Oncologie Cellulaire et Moleculaire Humaine, BPBS, 129 route de Stalingrad Bobigny, 93000 France.

ABSTRACT: Somatostatin (SS) can inhibit growth hormone (GH) secretion from the pituitary and tumor cell proliferation via membrane-bound receptors (SST). Five SST subtypes have been cloned and can be discriminated by specific peptides. In order to evaluate the human tissue distribution of the SSTs, we first used the cross-linking assay with the (125)I-SS-14. A cross- linked complex of 57 kDa was detected in a majority (76%) of the surgical biopsies of normal and tumoral tissues examined (N = 222) and in all tested cell lines (N = 20). However, in regard to the organs, the incidence varied from 33% (epiploon metastases) to 100% (colorectal adenocarcinoma, prostate). Additional, minor SS-14 cross-linked complexes were detected in a few samples, suggesting the simultaneous existence of other SST subtypes. In tumor cell lines, the 57-kDa complex was reduced by the SST2-selective SS analogs BIM23014, BIM23060, and BIM23068, and by SS-14 but not by the non-SST2-selective BIM23052 and BIM23056. Its pharmacological profile therefore corresponded to SST2. Northern blot analysis showed one 2.5- kb human SST2 mRNA in these cell lines. We demonstrate that SST2 is detectable in normal and tumoral human tissues and thus represents an SST subtype target for the development of more specific SS analogs.

KEY WORDS: somatostatin-14, tissue, receptor, cross-linking assay.

http://www.cancerprev.org/Journal/Issues/21/1/171