6752

SSTR2

somatostatin receptor 2;SSTR2;somatostatin receptor 2

SRIF-1|SS2R|somatostatin receptor type 2

17q24

protein-coding

BACKGROUND: The management of pulmonary neuroendocrine tumours (NETs), with special reference to clinically aggressive carcinoids and large-cell neuroendocrine carcinomas (LCNECs), is poorly standardised and data about somatostatin receptor (SSTR) expression or therapeutic guidelines for somatostatin analogue administration are still debated. MATERIALS AND METHODS: A series of 218 lung NETs [24 metastatic typical carcinoids (TCs), 73 atypical carcinoids (ACs), 60 LCNECs and 61 surgically resected small-cell lung carcinomas] were investigated for SSTR types 2A and 3 tissue distribution using immunohistochemistry, in correlation with clinicopathologic parameters, outcome, scintigraphy and treatment. RESULTS: SSTRs were heterogeneously distributed with a significant progressive decrease from low- to high-grade forms. SSTR type 2A was strikingly overexpressed in metastatic TCs as compared with ACs and clinically benign TCs. SSTR tissue immunolocalization correlated with octreotide scintigraphy in 20 of 28 cases. CONCLUSION: The immunohistochemical determination of SSTRs, with special reference to low-grade/intermediate-grade tumours, may assist the clinical approach with somatostatin analogue-based diagnostic and therapeutic procedures in clinically aggressive pulmonary NETs.

AIM: To investigate the anti-angiogenic effect of somatostatin receptor subtype 2 (SSTR2) gene transfer into pancreatic cancer cell line PC-3, and the mechanisms involved in this effect. METHODS: The full length human SSTR2 cDNA was introduced into pancreatic cancer cell line PC-3 by lipofectamine-mediated transfection. Positive clones were screened by G418 and stable expression of SSTR2 was detected by immunohistochemistry SABC methods and RT-PCR. Enzyme-linked immunosorbent assay (ELISA) was used to detect vascular endothelial growth factor (VEGF) levels in the cell culture supernatants of SSTR2-expressing cells, vector control and mock control cells. Furthermore, the expressions of VEGF and matrix metalloproteinase-2 (MMP-2) were detected by immunohistochemistry SABC methods and RT-PCR in these cells. RESULTS: VEGF levels in the cell culture supernatants were significantly reduced in the SSTR2-expressing cells (first week, 172.63+/-21.2 ng/L and after two months, 198.85+/-26.44 ng/L) compared with the vector control (first week, 790.39+/-86.52 ng/L and after two months, 795.69+/-72.35 ng/L) and mock control (first week, 786.42+/-90.62 ng/L and after two months, 805.32+/-84.36 ng/L) (P<0.05). The immunohistochemical assay showed a significant reduction of the integral optical density of VEGF and MMP-2 in the SSTR2-expressing cells (42.25+/-8.6 and 70.5+/-6.25, respectively) compared with the vector control (85.75+/-12.9 and 110.52+/-13.5, respectively) and mock control (82.6+/-9.28 and 113.56+/-9.62, respectively) (P<0.05). Conversely, the average gray value of VEGF and MMP-2 was significantly increased in the SSTR2-expressing cells (121.56+/-8.43 and 134.46+/-19.95, respectively) compared with the vector control (55.72+/-5.6 and 62.26+/-12.68, respectively) and mock control cells (58.48+/-6.2 and 65.49+/-9.16, respectively) (P<0.05). Moreover, the expressions of VEGF mRNA and MMP-2 mRNA were significantly reduced in the SSTR2-expressing cells (0.1384+/-0.017 and 0.2343+/-0.070, respectively) compared with the vector control (1.024+/-0.117 and 0.806+/-0.119, respectively) and mock control (1.085+/-0.105 and 0.714+/-0.079, respectively) (P<0.05). CONCLUSION: The expression of reintroduced human SSTR2 gene exerts its antiangiogenic effects by down-regulating the expressions of the factors involved in tumor angiogenesis and metastasis, suggesting SSTR2 gene transfer as a new strategy of gene therapy for pancreatic cancer.