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

¹ Service of Gastroentérologie-Pancréatologie, Pôle de maladies de l’appareil Digestif and ² Service of Anatomo-pathologie, Hôpital Beaujon, Clichy, France, ³ Laboratory Interactions Cellulaires Neuroendocriniennes, CNRS-UMR6544, Institut Fédératif Jean-Roche, Faculté de Médecine Nord, Université de la Méditerranée, Marseille, France and ⁴ Laboratory of Biochemistry and Molecular Biology, Centre Hospitalo-Universitaire Conception, Marseille, France

(Correspondence should be addressed to A Barlier at Laboratory Interactions Cellulaires Neuroendocriniennes, CNRS-UMR6544, Institut Fédératif Jean-Roche, Marseille, France; Email: barlier.a{at}jean-roche.univ-mrs.fr)

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 real-time 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 nonfunctional 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 x 10^–2 vs 69.7 ± 19.5 x 10^–2 copy/copy ß-Gus (P < 0.0036) and 519.6 ± 121.2 x 10^–2 vs 50.0 ± 21.6 x 10^–2 copy/copy ß-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.

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