The neuroblastoma cell line, SKNSH, expresses mRNA for sst1, sst2, and sst4 as identified by RT-PCR. However, no receptor protein can be identified by Western blot or by competitive binding. We hypothesized that upregulation of somatostatin receptors would regulate the rate of cell proliferation. Isogenic SKNSH cell lines expressing sst1 or sst2 were generated by transfection followed by subcloning. SKNSH, SKNSH/sst1 and SKNSH/ssst2 cell lines were then cultured in vitro and injected subcutaneously in the hind limb of nude mice.

The rate of cell proliferation of SKNSH/sst2 cells was decreased by 62% compared to SKNSH cells. This decrease in cell growth was associated with upregulation of somatostatin gene expression. Similarly, the rate of generation of subcutaneous tumors in nude mice was decreased in SKNSH/sst2 cells compared to the SKNSH cell line. In contrast, upregulation of sst1 in SKNSH/sst1 cells was not associated with any decrease in either in vitro or in vivo cell proliferation.

These results suggest that expression of sst2 regulates endogenous expression of somatostatin in the SKNSH neuroblastoma cell line; further, co-expression of sst2 and somatostatin regulates the rate of cell proliferation, both in vitro and in vivo.

Funded by the National Cancer Institute (R01 CA64177) to MSO.