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<PubmedArticle><MedlineCitation Status="Publisher" Owner="NLM"><PMID Version="1">39665969</PMID><DateRevised><Year>2024</Year><Month>12</Month><Day>12</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1532-7361</ISSN><JournalIssue CitedMedium="Internet"><PubDate><Year>2024</Year><Month>Dec</Month><Day>10</Day></PubDate></JournalIssue><Title>Surgery</Title><ISOAbbreviation>Surgery</ISOAbbreviation></Journal><ArticleTitle>GLP-1R agonist promotes proliferation of neuroendocrine neoplasm cells expressing GLP-1 receptors.</ArticleTitle><Pagination><StartPage>108943</StartPage><MedlinePgn>108943</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.surg.2024.09.052</ELocationID><ELocationID EIdType="pii" ValidYN="Y">S0039-6060(24)00915-2</ELocationID><Abstract><AbstractText Label="OBJECTIVES" NlmCategory="OBJECTIVE">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.</AbstractText><AbstractText Label="METHODS" NlmCategory="METHODS">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.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">BON, NEC1452, and NEC1583&#xa0;cells expressed significantly lower levels of GLP-1R transcript and protein than GOT1, NT-3, and NEC913&#xa0;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%.</AbstractText><AbstractText Label="CONCLUSION" NlmCategory="CONCLUSIONS">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.</AbstractText><CopyrightInformation>Copyright &#xa9; 2024 Elsevier Inc. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Shilyansky</LastName><ForeName>Jonathan S</ForeName><Initials>JS</Initials><AffiliationInfo><Affiliation>Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chan</LastName><ForeName>Casandro J</ForeName><Initials>CJ</Initials><AffiliationInfo><Affiliation>Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xiao</LastName><ForeName>Sophia</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gribovskaja-Rupp</LastName><ForeName>Irena</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Quelle</LastName><ForeName>Dawn E</ForeName><Initials>DE</Initials><AffiliationInfo><Affiliation>Department of Pharmacology and Neuroscience, University of Iowa Carver College of Medicine, Iowa City, IA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Howe</LastName><ForeName>James R</ForeName><Initials>JR</Initials><AffiliationInfo><Affiliation>Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dillon</LastName><ForeName>Joseph S</ForeName><Initials>JS</Initials><AffiliationInfo><Affiliation>Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ear</LastName><ForeName>Po Hien</ForeName><Initials>PH</Initials><AffiliationInfo><Affiliation>Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA. Electronic address: pohien-ear@uiowa.edu.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2024</Year><Month>12</Month><Day>10</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Surgery</MedlineTA><NlmUniqueID>0417347</NlmUniqueID><ISSNLinking>0039-6060</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><CoiStatement>Conflict of Interest/Disclosure The authors declare no conflict of interest.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2024</Year><Month>5</Month><Day>15</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2024</Year><Month>9</Month><Day>13</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2024</Year><Month>9</Month><Day>25</Day></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2024</Year><Month>12</Month><Day>12</Day><Hour>12</Hour><Minute>29</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2024</Year><Month>12</Month><Day>12</Day><Hour>12</Hour><Minute>29</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2024</Year><Month>12</Month><Day>12</Day><Hour>11</Hour><Minute>13</Minute></PubMedPubDate></History><PublicationStatus>aheadofprint</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">39665969</ArticleId><ArticleId IdType="doi">10.1016/j.surg.2024.09.052</ArticleId><ArticleId IdType="pii">S0039-6060(24)00915-2</ArticleId></ArticleIdList></PubmedData></PubmedArticle></PubmedArticleSet>