CHARACTERIZATION OF SOMATOSTATIN RECEPTORS ON HUMAN NEUROBLASTOMA TUMORS

Neuroblastoma is the most common extracranial solid tumor of children. Neuroblastoma tumors derive from the neural crest and synthesize neur otransmitters including the neuropeptide somatostatin. This study was designed to characterize somatostatin receptors both in primary neurob lastoma tumors and in two neuroblastoma cell lines, SKNSH and IMR32. S omatostatin receptors were identified in 6 of 7 Stage I and II compare d to 7 of 19 Stage III and IV tumors. Down-regulation of somatostatin receptor binding was observed in five tumors during disease progressio n. A lack of high affinity binding of somatostatin was identified as a poor prognostic indicator; negative binding correlated with advanced disease and death. Somatostatin receptor binding was observed in the I MR32 cell line, but not in the SKNSH cell line. IMR32 cells demonstrat ed a single class of high affinity binding sites for both somatostatin and a synthetic analogue, octreotide (K(d) 0.16 +/- 0.05 nm and 0.89 +/- 0.23 nm, respectively). Somatostatin and octreotide inhibited both vasoactive intestinal peptide-mediated and forskolin-mediated cyclic AMP accumulation in IMR32 cells. Somatostatin and octreotide inhibitio n of signal transduction was attenuated by pretreatment of the cells w ith pertussis toxin. Octreotide inhibited proliferation of IMR32 cells by 70% in a 6-day culture. In contrast, octreotide did not exhibit hi gh affinity binding in SKNSH cells and had no effect on cyclic AMP acc umulation or on proliferation in SKNSH cells. Together, these data ind icate that octreotide interacts with high affinity somatostatin recept ors to modulate signal transduction and regulate proliferation in neur oblastoma cell lines. These data also suggest that somatostatin recept or expression may be an independent prognostic factor in primary neuro blastoma tumors.