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Int J Cancer. 2019 Mar 1;144(5):1104-1114. doi: 10.1002/ijc.31771. Epub 2018 Oct 9.

Somatostatin receptor 2 signaling promotes growth and tumor survival in small-cell lung cancer.

Author information

1
Division of Medical Oncology, Vanderbilt Ingram Cancer Center, Nashville, TN.
2
Cancer Early Detection and Prevention Initiative, Vanderbilt Ingram Cancer Center, Nashville, TN.
3
Veterans Affairs, Tennessee Valley Healthcare System, Nashville Campus, Nashville, TN.
4
Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt Ingram Cancer Center, Nashville, TN.
5
University of Tennessee Graduate School of Medicine, Tennessee Valley Healthcare System, Nashville Campus, Nashville, TN.
6
Vanderbilt University School of Medicine, Tennessee Valley Healthcare System, Nashville Campus, Nashville, TN.
7
Department of Pathology, Microbiology and Immunology, Tennessee Valley Healthcare System, Nashville Campus, Nashville, TN.
8
Vanderbilt University Department of Biostatistics, Tennessee Valley Healthcare System, Nashville Campus, Nashville, TN.

Abstract

Somatostatin receptor 2 (SSTR2) is overexpressed in a majority of neuroendocrine neoplasms, including small-cell lung carcinomas (SCLCs). SSTR2 was previously considered an inhibitory receptor on cell growth, but its agonists had poor clinical responses in multiple clinical trials. The role of this receptor as a potential therapeutic target in lung cancer merits further investigation. We evaluated the expression of SSTR2 in a cohort of 96 primary tumors from patients with SCLC and found 48% expressed SSTR2. Correlation analysis in both CCLE and an SCLC RNAseq cohort confirmed high-level expression and identified an association between NEUROD1 and SSTR2. There was a significant association with SSTR2 expression profile and poor clinical outcome. We tested whether SSTR2 expression might contribute to tumor progression through activation of downstream signaling pathways, using in vitro and in vivo systems and downregulated SSTR2 expression in lung cancer cells by shRNA. SSTR2 downregulation led to increased apoptosis and dramatically decreased tumor growth in vitro and in vivo in multiple cell lines with decreased AMPKα phosphorylation and increased oxidative metabolism. These results demonstrate a role for SSTR2 signaling in SCLC and suggest that SSTR2 is a poor prognostic biomarker in SCLC and potential future therapeutic signaling target.

KEYWORDS:

cancer progression; somatostatin; survival

PMID:
30152518
PMCID:
PMC6448409
[Available on 2020-03-01]
DOI:
10.1002/ijc.31771
[Indexed for MEDLINE]

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