Somatostatin receptor gene expression in neuroblastoma

Somatostatin receptor expression is a favorable prognostic factor in human neuroblastoma. Somatostatin receptors have been demonstrated in vitro by ph armacologic analysis of tumor tissue and in vivo by diagnostic radiorecepto r scintigraphy. However, which receptor subtypes (sst(1), sst(2), sst(3), s st(4), and sst(5)) are expressed in these tumors has not yet been delineate d. We used RT-PCR to analyze expression of the five somatostatin receptor g enes in 32 neuroblastoma tumor specimens. All 32 tumor specimens expressed mRNA for c-abl and sst(1); sst(2) mRNA was detected in 27/32 samples and so matostatin mRNA was detected in 30/32 tumor specimens. The remaining recept or subtypes, sst(3), sst(4), and sst(5) were variably expressed. Receptor p rotein for sst(1) and sst(2) was visualized in tumor neuroblasts as well as in endothelial cells of tumor vessels using immunostaining with specific a nti-receptor antibodies. The effect of high expression of somatostatin rece ptors on cell proliferation was examined in SKNSH neuroblastoma cells trans fected with sst(1) and sst(2). SS14 binding to wild-type SKNSH cells was un detectable; but the native peptide bound with high affinity to the SKNSH/ss t(1) and SKNSH/sst(2), neuroblastoma cell lines. Pharmacologic analysis of binding with two long-acting analogues, CH275 and octreotide, confirmed sel ective expression of sst(1) and sst(2) in stably transfected SKNSH cells. F ormation of neuroblastoma xenograft tumors in nude mice was significantly d elayed for both SKNSH/sst(1) (P < 0.001) and SKNSH/sst(2) (P < 0.05) cells compared to wild-type SKNSH. We conclude that: (1) Somatostatin receptors, sst(1) and sst(2), an expressed in the majority of neuroblastomas at diagno sis; and (2) upregulation of functional sst(1) or sst(2) in neuroblastoma c ell lines suppresses tumorigenicity in a xenograft model. These observation s suggest that somatostatin receptors may be a useful therapeutic target in neuroblastoma. (C) 2000 Elsevier Science B.V. All rights reserved.