Journal article
Metastatic pancreatic neuroendocrine tumors have decreased somatostatin expression and increased Akt signaling
Surgery, Vol.169(1), pp.155-161
01/01/2021
DOI: 10.1016/j.surg.2020.04.034
PMCID: PMC7736292
PMID: 32611516
Abstract
Background: Patients with pancreatic neuroendocrine tumors often present with metastases, which reduce survival. Molecular features associated with pancreatic neuroendocrine tumor tumorigenesis have been reported, but mechanisms of metastasis remain incompletely understood.
Methods: RNA sequencing was performed on primary and metastatic pancreatic neuroendocrine tumors from 43 patients. Differentially expressed genes were identified, and quantitative polymerase chain reaction used to confirm expression differences. BON cells were transfected with short interfering RNAs and short hairpin RNAs to create knockdowns. Expression changes were confirmed by quantitative polymerase chain reaction, cell viability assessed, and protein levels evaluated by Western blot and immunofluorescence.
Results: Nodal and hepatic metastases had decreased expression of somatostatin compared with primary tumors (P = .003). Quantitative polymerase chain reaction in a validation cohort confirmed 5.3-fold lower somatostatin expression in hepatic metastases (P = .043) with no difference in somatostatin receptor, synaptophysin, or chromogranin A expression. Somatostatin knockdown in BON cells increased cell metabolic activity, viability, and growth. Somatostatin-knockdown cells had significantly higher levels of phosphorylated Akt protein and higher mTOR compared with controls.
Conclusion: Pancreatic neuroendocrine tumor metastases have lower expression of somatostatin than primary tumors, and somatostatin knockdown increased growth in pancreatic neuroendocrine tumor cell lines. This was associated with increased activation of Akt, identifying this pathway as a potential mechanism by which loss of somatostatin expression promotes the metastatic phenotype. (C) 2020 Elsevier Inc. All rights reserved.
Details
- Title: Subtitle
- Metastatic pancreatic neuroendocrine tumors have decreased somatostatin expression and increased Akt signaling
- Creators
- Catherine G. Tran - University of IowaAaron T. Scott - Roy J. and Lucille A. Carver College of MedicineGuiying Li - University of IowaScott K. Sherman - Roy J. and Lucille A. Carver College of MedicinePo Hien Ear - Roy J. and Lucille A. Carver College of MedicineJames R. Howe - Roy J. and Lucille A. Carver College of Medicine
- Resource Type
- Journal article
- Publication Details
- Surgery, Vol.169(1), pp.155-161
- DOI
- 10.1016/j.surg.2020.04.034
- PMID
- 32611516
- PMCID
- PMC7736292
- NLM abbreviation
- Surgery
- ISSN
- 0039-6060
- eISSN
- 1532-7361
- Publisher
- Elsevier
- Number of pages
- 7
- Grant note
- P50 CA174521 / SPORE NANETS BTSI award T32CA148062; T32CA078586 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 01/01/2021
- Academic Unit
- Surgery; Internal Medicine
- Record Identifier
- 9984322801102771
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