The analysis of quantitative expression of somatostatin and dopamine receptors in gastro-entero-pancreatic tumours opens new therapeutic strategies.
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 D(2). New chimeric analogues simultaneously recognising sst(2) and sst(5) or sst(2) and D(2) have additive effects in inhibition of GH and prolactin secretion in pituitary adenomas. Our aim was to quantify the expression of sst and D(2) mRNA in human GEP tumours.


METHODS
mRNA expression of sst(1), sst(2), sst(3) and sst(5) as well as D(2), 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 sst(1), sst(2) and D(2). Expression of sst(3) and sst(5) was observed in 89 and 76% of tumours respectively with highly variable levels. sst(2) mRNA expression was higher in nonfunctional tumours (P < 0.009) and sst5 was higher in pancreatic than in intestinal tumours (P < 0.02). Whereas sst(2) levels were similar between GEP and somatotroph tumours, levels of sst(5) and D(2) were higher in the former (394.9 +/- 156.1 x 10(-2) vs 69.7 +/- 19.5 x 10(-2) copy/copy beta-Gus (P < 0.0036) and 519.6 +/- 121.2 x 10(-2) vs 50.0 +/- 21.6 x 10(-2) copy/copy beta-Gus (P < 0.0001) respectively). In small tumours ( < 30 mm), sst(2) 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 sst(3) 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 sst(2) and D(2) in 100% of cases and sst(5) in 89% thus supporting the testing of bi-specific agonists (sst(2)/sst(5) or sst(2)/D(2)) in these tumours.
O'Toole
Dermot
D
Service of Gastroentérologie-Pancréatologie, Pôle de Maladies de l'Appareil Digestif, Hôpital Beaujon, Clichy, France.
Saveanu
Alexandru
A
Couvelard
Anne
A
Gunz
Ginette
G
Enjalbert
Alain
A
Jaquet
Philippe
P
Ruszniewski
Philippe
P
Barlier
Anne
A
D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000235:genetics; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D010911:Pituitary Neoplasms / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000235:genetics*; D017481:Receptors, Somatostatin / Q000819:agonists / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D017481:Receptors, Somatostatin; D042461:Vascular Endothelial Growth Factor A; C103631:somatostatin receptor 3; C094573:somatostatin receptor 5; C093733:somatostatin receptor 2