Panoply™ Human SSTR2 Knockdown Stable Cell Line

Somatostatin receptor 2 (SSTR2) is overexpressed in most neuroendocrine tumors, including small cell lung cancer (SCLC). SSTR2 was previously considered an inhibitory receptor for cell growth, but its agonists have yielded poor clinical responses in multiple clinical trials. Here, researchers evaluated SSTR2 expression in primary tumors from 96 SCLC patients and found that 48% expressed SSTR2. Correlation analysis in CCLE and SCLC RNAseq cohorts confirmed elevated SSTR2 expression and identified an association between NEUROD1 and SSTR2. SSTR2 expression profiles were significantly associated with poor clinical prognosis. In multiple cell lines with decreased AMPKα phosphorylation and enhanced oxidative metabolism, SSTR2 downregulation led to increased apoptosis and significantly suppressed tumor growth in vitro and in vivo. These results confirm a role for SSTR2 signaling in SCLC and suggest that SSTR2 is a biomarker for poor prognosis in SCLC and a potential future therapeutic target.

Cleaved effector caspases 3, 7, and 9 were increased in SSTR2 knockdown H1048 cells (Figure 1A). This increased apoptotic milieu was not observed in the atypical carcinoid cell line H727 (Figure 1B). Global changes in BCL family expression were also observed with loss of SSTR2. Flow cytometry confirmed expected changes in apoptosis with SSTR2 knockdown H1048 cells, demonstrating increased apoptosis and changes in cell cycling with a significantly increased pre G1 phase (Figure 1C). After SSTR2 knockdown, H1048 cells showed increased pAKT levels and stable pERK levels. Overall, significant differences in downstream signaling events and apoptosis were observed between the H1048 shRNA scrambled control and SSTR2 knockdown cell lines, consistent with decreased cell viability caused by SSTR2 loss of function.

Figure 1. Loss of SSTR2 leads to increased cleaved caspase and apoptosis. (Lehman J M, et al., 2019)