DETECTION OF SOMATOSTATIN RECEPTOR SUBTYPE-2 (SSTR2) IN ESTABLISHED TUMORS AND TUMOR-CELL LINES - EVIDENCE FOR SSTR2 HETEROGENEITY

The somatostatin receptor subtype 2 (SSTR2) was detected in a wide ran ge of human and rat tumors using in vitro receptor binding ([I-125]MK- 678), receptor gene expression analysis, and immunoblotting techniques . The highest receptor concentrations were observed in the rat AR42J p ancreatic and human small cell lung cancer (SCLC) cell lines, NCI-H69 and NCI-H345, with much lower levels detected in breast, prostate, mel anoma, and hepatic tumors. Several human pancreas tumors were devoid o f SSTR2. For all tumors showing detectable [I-125]MK-678 binding, SSTR 2 receptor mRNA was expressed. Furthermore, a mRNA transcript correspo nding to a truncated isoform of SSTR2 was detected at low levels in th e human SCLC NCI-H69 cell line, and likely represents a human homologu e of rodent SSTR2B. Immunoblotting analysis using the SSTR2-specific a ntibody, 2e3, detected multiple immunoreactive protein species, includ ing a predominant 150-kDa molecule, which could be blocked by the SSTR 2-derived 2e3 peptide. Somatostatin (SRIF) peptides with high SSTR2 af finity and antiproliferative properties were potent inhibitors of [I-1 25]MK-678 binding to several tumor types, suggesting that they may exe rt antitumor effects via the SSTR2 receptor.