The analysis of quantitative expression of somatostatin and dopamine receptors in gastro-entero-pancreatic tumours opens new therapeutic strategies

Abstract

Objective: Somatostatin (sst) are present in the majority of gastro-entero-pancreatic (GEP) tumours. Effects of somatostatin receptor (sst) analogues are partial and of limited duration. Cell lines derived from GEP express dopaminergic receptors D2. New chimeric analogues simultaneously recognising SSt2 and SSt5 or SSt2 and D2 have additive effects in inhibition of GH and prolactin secretion in pituitary adenomas. Our aim was to quantify the expression of sst and D2 mRNA in human GEP tumours. Design and methods: mRNA expression of sst1, sst2, sst3 and sst5 as well as D2, was analysed using realtime PCR (TaqMan probe) in a series of 35 patients with GEP tumours (pancreas (n = 19) and intestinal (n = 16)). Levels of expression were compared with a group of 13 somatotroph adenomas. Results: All GEP tumours express sst1, sst2 and D2. Expression of sst3 and sst5 was observed in 89 and 76% of tumours respectively with highly variable levels. sst2 mRNA expression was higher in non-functional tumours (P<0.009) and sst5 was higher in pancreatic than in intestinal tumours (P<0.02). Whereas sst2 levels were similar between GEP and somatotroph tumours, levels of sst5 and D2 were higher in the former (394.9±156.1 × 10-2 vs 69.7±19.5 × 10-2 copy/ copy Β-Gus (P<0.0036) and 519.6±121.2 × 10-2 vs 50.0±21.6 × 10-2 copy/copy Β-Gus (P<0.0001) respectively). In small tumours (<30 mm), sst2, density appeared as a crucial parameter in somatostatin receptor scintigraphy results, whereas in big tumours, a consistent bias in SRS results was introduced by the size. In pancreatic GEP, high-level sst3 expression was found in tumours with more active angiogenesis (higher microvessel density and vascular endothelial growth factor expression (P<0.03)). Conclusions: GEP tumours co-express sst2 and D2 in 100% of cases and sst5 in 89% thus supporting the testing of bi-specific agonists (sst2/sst5 or sst2/D2) in these tumours. © 2006 Society of the European Journal of Endocrinology.