Journal article
GLP-1R agonist promotes proliferation of neuroendocrine neoplasm cells expressing GLP-1 receptors
Surgery, Vol.179, 108943
03/2025
DOI: 10.1016/j.surg.2024.09.052
PMID: 39665969
Abstract
Semaglutide is a glucagon-like peptide 1 (GLP-1) analog that binds to GLP-1 receptors (GLP-1R) on beta-cells and neuronal cells and is used for treating type 2 diabetes and obesity. Insulin-secreting pancreatic neuroendocrine neoplasms have been reported to express high levels of GLP-1R protein, raising the possibility that GLP-1 receptor agonists could promote tumor growth. Our goal was to quantify GLP-1R expression levels in 6 neuroendocrine neoplasm cellular models and determine their proliferative response to semaglutide treatment.
Gene expression of GLP-1R in neuroendocrine neoplasm cells (BON, GOT1, NT-3, NEC913, NEC1452, and NEC1583) was measured by quantitative polymerase chain reaction. Protein expression was determined by immunofluorescent staining and Western blotting. Neuroendocrine neoplasm cells were incubated with semaglutide, and cell growth was measured using a cell viability assay. Mice harboring GOT1 xenografts were treated with semaglutide, and tumor volumes were measured.
BON, NEC1452, and NEC1583 cells expressed significantly lower levels of GLP-1R transcript and protein than GOT1, NT-3, and NEC913 cells. GOT1 and NT-3 showed the highest response to semaglutide treatment, with a 19% and 22% increase in growth. Semaglutide promotes tumor growth in mice with GOT1 xenografts by 72%.
The impact of the GLP-1 receptor agonist semaglutide on neuroendocrine cancer growth is understudied. Our data revealed that 50% of neuroendocrine neoplasm cell lines tested expressed GLP-1R, and semaglutide treatment promoted their growth. These results indicate a potential risk in the use of semaglutide in patients with neuroendocrine neoplasms expressing GLP-1R. Investigations into a larger set of neuroendocrine neoplasms would be important because they are highly heterogeneous.
Details
- Title: Subtitle
- GLP-1R agonist promotes proliferation of neuroendocrine neoplasm cells expressing GLP-1 receptors
- Creators
- Jonathan S Shilyansky - University of IowaCasandro J Chan - Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IASophia Xiao - Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IAIrena Gribovskaja-Rupp - University of IowaDawn E Quelle - University of IowaJames R Howe - University of IowaJoseph S Dillon - University of IowaPo Hien Ear - Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA. Electronic address: pohien-ear@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- Surgery, Vol.179, 108943
- Publisher
- Elsevier
- DOI
- 10.1016/j.surg.2024.09.052
- PMID
- 39665969
- ISSN
- 0039-6060
- eISSN
- 1532-7361
- Grant note
- University of Iowa Holden Comprehensive Cancer Center
We are grateful for support from the University of Iowa Holden Comprehensive Cancer Center. We thank Drs Mark Evers, Jorg Shrader, Ola Nilsson, and Yvonne Arvidsson for the BON, NT-3, and GOT1 cells. In addition, we thank Dr Shujie Yang for generously donating NSG mice for this study.
- Language
- English
- Electronic publication date
- 12/10/2024
- Date published
- 03/2025
- Academic Unit
- Pathology; Orthopedics and Rehabilitation; Surgery; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984757269202771
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