Re: Expression of Somatostatin Receptor Subtype 1–5 Genes in Human Pancreatic Cancer

Extract

Recently, Fisher et al. (1) examined messenger RNA (mRNA) expression of the somatostatin receptor subtypes (sst1–5) in 11 specimens of pancreatic adenocarcinoma tissues and nine human pancreatic cancer cell lines. Several tumors and cell lines expressed multiple subtypes, including sst1, sst2, and sst5. However, only one cell line (MIA PaCa2) displayed high-affinity binding sites for somatostatin-14. Fisher et al. concluded that a defect of receptor protein expression at the cell surface in pancreatic cancers could provide an explanation for the failure of somatostatin analogues to delay tumor progression as observed in clinical trials.

We previously demonstrated that the receptor sst2 mediated the antiproliferative effect of somatostatin analogues in vitro, through the activation of the tyrosine phosphatase SHP1 (2,3). It is interesting that we and Fisher et al. found that the sst2 subtype was expressed in MIA PaCa-2 cells grown in vitro (4) or in vivo (by xenograft into athymic mice) (5). Expression of sst2 in MIA PaCa-2 cells correlates well with 1) the high affinity of RC-160 (a somatostatin analogue) for somatostatin receptors described in these cells (6) and 2) the antiproliferative effect of the treatment with this analogue for both in vitro cell culture and in vivo in the xenograft model (6). We previously evaluated the sst1–5 mRNA expression on both primary and metastatic pancreatic adenocarcinoma specimens and human pancreatic cell lines by use of reverse transcription and polymerase chain reaction (4). We also detected the presence of multiple sst mRNAs but, in comparison with normal pancreatic tissue specimens, we observed a specific loss of sst2 subtype expression in tumor tissues and in most of the cell lines tested. We thus concluded that the loss of sst2 expression in pancreatic cancer could confer a growth advantage for these tumors and could provide one of the explanations for the frequent lack of therapeutic effect of somatostatin analogues administered in such adenocarcinomas. We confirmed this hypothesis after stable transfection of human sst2 in the two pancreatic cell lines BxPC-3 and Capan-1 (both did not express sst2 normally), resulting in the decrease or suppression of both in vitro and in vivo tumorigenicity (7).