Abstract
The somatostatin receptor subtype 2 (SSTR2) was detected in a wide range of human and rat tumors using in vitro receptor binding ([ 125I]MK-678), receptor gene expression analysis, and immunoblotting techniques. The highest receptor concentrations were observed in the rat AR42J pancreatic and human small cell lung cancer (SCLC) cell lines, NCI-H69 and NCI-H345, with much lower levels detected in breast, prostate, melanoma, and hepatic tumors. Several human pancreas tumors were devoid of SSTR2. For all tumors showing detectable [ 125I]MK-678 binding, SSTR2 receptor mRNA was expressed. Furthermore, a mRNA transcript corresponding to a truncated isoform of SSTR2 was detected at low levels in the human SCLC NCI-H69 cell line, and likely represents a human homologue of rodent SSTR2B. Immunoblotting analysis using the SSTR2-specific antibody, 2e3, detected multiple immunoreactive protein species, including a predominant 150-kDa molecule, which could be blocked by the SSTR2-derived 2e3 peptide. Somatostatin (SRIF) peptides with high SSTR2 affinity and antiproliferative properties were potent inhibitors of [ 125I]MK-678 binding to several tumor types, suggesting that they may exert antitumor effects via the SSTR2 receptor.
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