Glucagon-Like Peptide-1 Receptor Expression in Normal and Neoplastic Human Pancreatic Tissues.
OBJECTIVE
Studies have proposed pro-oncogenic effects of glucagon-like peptide-1 receptor (GLP-1R) agonists in the pancreas by promoting GLP-1R overactivation in pancreatic cells. However, the expression of GLP-1R in normal and neoplastic pancreatic cells remains poorly defined, and reliable methods for detecting GLP-1R in tissue specimens are needed.


METHODS
We used RNA in situ hybridization to quantify glp-1r RNA in surgically resected human pancreatic specimens, including pancreatic ductal adenocarcinoma (PDAC), preinvasive intraepithelial lesions (pancreatic intraepithelial neoplasia), and non-neoplastic ductal, acinar, and endocrine cells. A mixed-effect linear regression model was used to investigate the relationship between glp-1r signals and all cells, ordered by increasing grade of dysplasia.


RESULTS
All cell types had evidence of glp-1r transcripts, with the highest expression in endocrine cells and lowest in ductal cells. The slope of the fitted line was not significantly different from zero (0.07; 95% confidence interval, -0.0094 to 0.244; P = 0.39), suggesting that progression from normal cells to PDAC is not associated with a parallel increase in glp-1r RNA. A series of pairwise comparisons between all cell types with respect to their glp-1r expression showed no significant difference in glp-1r in cancer, pancreatic intraepithelial neoplasia, and acinar and ductal cells.


CONCLUSIONS
Our study supports the lack of evidence for GLP-1R overexpression in PDAC.
From the *Department of Pathology, the Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, Baltimore, MD; †Department of Pathology, Seoul National University College of Medicine, Seoul, South Korea; and the Departments of ‡Oncology and §Medicine, the Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, Baltimore, MD.
Marco
M
Dal Molin
Haeryoung
H
Kim
Amanda
A
Blackford
Rajni
R
Sharma
Michael
M
Goggins
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015820:Cadherins / Q000032:analysis; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D000067757:Glucagon-Like Peptide-1 Receptor / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000166:cytology / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D012334:RNA, Neoplasm / Q000235:genetics; D046888:Tissue Array Analysis
D015820:Cadherins; D000067757:Glucagon-Like Peptide-1 Receptor; D012334:RNA, Neoplasm