THE SOMATOSTATIN RECEPTOR SUBTYPE-2 IS EXPRESSED IN NORMAL AND TUMORAL HUMAN TISSUES

Somatostatin (SS) can inhibit growth hormone (GH) secretion hom the pi tuitary and tumor cell proliferation via membrane-bound receptors (SST ). Five SST subtypes have been cloned and can be discriminated by spec ific peptides. In order to evaluate the human tissue distribution of t he SSTs, we first used the cross-linking assay with the I-125-SS-14. A cross-linked complex of 57 kDa was detected in a majority (76%) of th e surgical biopsies of normal and tumoral tissues examined (N = 222) a nd in all tested cell lines (N = 20). However. in regard to the organs , the incidence varied from 33% (epiploon metastases) to 100% (colorec tal adenocarcinoma, prostate). Additional, minor SS-14 cross-linked co mplexes were detected in a few samples, suggesting the simultaneous ex istence 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 h uman tissues and thus represents an SST subtype target for the develop ment of more specific SS analogs.