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Article

Significance of expression of glucagon-like peptide 1 receptor in pancreatic cancer

  • Authors:
    • Ana Ines Cases
    • Takao Ohtsuka
    • Hideyo Kimura
    • Biao Zheng
    • Koji Shindo
    • Yoshinao Oda
    • Kazuhiro Mizumoto
    • Masafumi Nakamura
    • Masao Tanaka
  • View Affiliations / Copyright

    Affiliations: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Higashi‑ku, Fukuoka 812‑8582, Japan, Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Higashi‑ku, Fukuoka 812-8582, Japan
  • Pages: 1717-1725
    |
    Published online on: July 20, 2015
       https://doi.org/10.3892/or.2015.4138
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Abstract

Glucagon-like peptide 1 (GLP-1) induces insulin secretion and proliferation of pancreatic β-cells, and inhibits their apoptosis through the GLP-1 receptor (GLP-1R), thus providing a foundation for using GLP-1-based therapies for the treatment of type 2 diabetes. However, doubts have emerged regarding the drug safety of these therapies. We investigated the potential role of GLP-1R in pancreatic ductal adenocarcinoma (PDAC). GLP-1R expression was semi-quantitatively evaluated by immunohistochemistry in 48 PDAC samples, and its correlations with clinicopathological features were investigated. CFPAC-1 cells were used for GLP-1R knockdown to evaluate its effects on cell proliferation, migration and invasion. GLP-1R expression was positive in 23 tumors and negative in 25 tumors. No correlations were found between GLP-1R expression status and clinicopathological characteristics. Furthermore, GLP-1R expression status did not affect the patient prognosis (P=0.74). The majority of lymph node metastases (11 of 15 samples examined; 73%) were positive for GLP-1R expression. Immunoreactivity for GLP-1R was also noted in sites of perineural and lymphovascular invasion. GLP-1R knockdown significantly reduced the proliferation, migration and invasion of CFPAC-1 cells (P<0.05). In conclusion, although GLP-1R is not an independent prognostic factor in PDAC patients, it appears to have some implications for PDAC metastatic ability.
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1 

Vincent A, Herman J, Schulick R, Hruban RH and Goggins M: Pancreatic cancer. Lancet. 378:607–620. 2011. View Article : Google Scholar : PubMed/NCBI

2 

Pierce KL, Premont RT and Lefkowitz RJ: Seven-transmembrane receptors. Nat Rev Mol Cell Biol. 3:639–650. 2002. View Article : Google Scholar : PubMed/NCBI

3 

Dorsam RT and Gutkind JS: G-protein-coupled receptors and cancer. Nat Rev Cancer. 7:79–94. 2007. View Article : Google Scholar : PubMed/NCBI

4 

Koehler JA and Drucker DJ: Activation of glucagon-like peptide-1 receptor signaling does not modify the growth or apoptosis of human pancreatic cancer cells. Diabetes. 55:1369–1379. 2006. View Article : Google Scholar : PubMed/NCBI

5 

Zhao H, Wang L, Wei R, Xiu D, Tao M, Ke J, Liu Y, Yang J and Hong T: Activation of glucagon-like peptide-1 receptor inhibits tumourigenicity and metastasis of human pancreatic cancer cells via PI3K/Akt pathway. Diabetes Obes Metab. 16:850–860. 2014. View Article : Google Scholar : PubMed/NCBI

6 

Zhao H, Wei R, Wang L, Tian Q, Tao M, Ke J, Liu Y, Hou W, Zhang L, Yang J, et al: Activation of glucagon-like peptide-1 receptor inhibits growth and promotes apoptosis of human pancreatic cancer cells in a cAMP-dependent manner. Am J Physiol Endocrinol Metab. 306:E1431–E1441. 2014. View Article : Google Scholar : PubMed/NCBI

7 

Ayoub WA, Kumar AA, Naguib HS and Taylor HC: Exenatide-induced acute pancreatitis. Endocr Pract. 16:80–83. 2010. View Article : Google Scholar

8 

Lee PH, Stockton MD and Franks AS: Acute pancreatitis associated with liraglutide. Ann Pharmacother. 45:e222011. View Article : Google Scholar : PubMed/NCBI

9 

Iyer SN, Drake AJ III, West RL, Mendez CE and Tanenberg RJ: Case report of acute necrotizing pancreatitis associated with combination treatment of sitagliptin and exenatide. Endocr Pract. 18:e10–e13. 2012. View Article : Google Scholar

10 

Elashoff M, Matveyenko AV, Gier B, Elashoff R and Butler PC: Pancreatitis, pancreatic, and thyroid cancer with glucagon-like peptide-1-based therapies. Gastroenterology. 141:150–156. 2011. View Article : Google Scholar : PubMed/NCBI

11 

Singh S, Chang HY, Richards TM, Weiner JP, Clark JM and Segal JB: Glucagonlike peptide 1-based therapies and risk of hospitalization for acute pancreatitis in type 2 diabetes mellitus: A population-based matched case-control study. JAMA Intern Med. 173:534–539. 2013. View Article : Google Scholar : PubMed/NCBI

12 

Matveyenko AV, Dry S, Cox HI, Moshtaghian A, Gurlo T, Galasso R, Butler AE and Butler PC: Beneficial endocrine but adverse exocrine effects of sitagliptin in the human islet amyloid polypeptide transgenic rat model of type 2 diabetes: Interactions with metformin. Diabetes. 58:1604–1615. 2009. View Article : Google Scholar : PubMed/NCBI

13 

Gier B, Matveyenko AV, Kirakossian D, Dawson D, Dry SM and Butler PC: Chronic GLP-1 receptor activation by exendin-4 induces expansion of pancreatic duct glands in rats and accelerates formation of dysplastic lesions and chronic pancreatitis in the KrasG12D mouse model. Diabetes. 61:1250–1262. 2012. View Article : Google Scholar : PubMed/NCBI

14 

Butler AE, Campbell-Thompson M, Gurlo T, Dawson DW, Atkinson M and Butler PC: Marked expansion of exocrine and endocrine pancreas with incretin therapy in humans with increased exocrine pancreas dysplasia and the potential for glucagon-producing neuroendocrine tumors. Diabetes. 62:2595–2604. 2013. View Article : Google Scholar : PubMed/NCBI

15 

Reubi JC: Peptide receptors as molecular targets for cancer diagnosis and therapy. Endocr Rev. 24:389–427. 2003. View Article : Google Scholar : PubMed/NCBI

16 

Cases AI, Ohtsuka T, Fujino M, Ideno N, Kozono S, Zhao M, Ohuchida K, Aishima S, Nomura M, Oda Y, et al: Expression of glucagon-like peptide 1 receptor and its effects on biologic behavior in pancreatic neuroendocrine tumors. Pancreas. 43:1–6. 2014. View Article : Google Scholar

17 

Nakamura T, Ito T, Uchida M, Hijioka M, Igarashi H, Oono T, Kato M, Nakamura K, Suzuki K, Jensen RT, et al: PSCs and GLP-1R: Occurrence in normal pancreas, acute/chronic pancreatitis and effect of their activation by a GLP-1R agonist. Lab Invest. 94:63–78. 2014. View Article : Google Scholar

18 

Hörsch D, Göke R, Eissele R, Michel B and Göke B: Reciprocal cellular distribution of glucagon-like peptide-1 (GLP-1) immunoreactivity and GLP-1 receptor mRNA in pancreatic islets of rat. Pancreas. 14:290–294. 1997. View Article : Google Scholar : PubMed/NCBI

19 

Waser B and Reubi JC: Radiolabelled GLP-1 receptor antagonist binds to GLP-1 receptor-expressing human tissues. Eur J Nucl Med Mol Imaging. 41:1166–1171. 2014. View Article : Google Scholar : PubMed/NCBI

20 

Furukawa T, Kuboki Y, Tanji E, Yoshida S, Hatori T, Yamamoto M, Shibata N, Shimizu K, Kamatani N and Shiratori K: Whole-exome sequencing uncovers frequent GNAS mutations in intraductal papillary mucinous neoplasms of the pancreas. Sci Rep. 1:1612011. View Article : Google Scholar :

21 

Sato N, Mizumoto K, Beppu K, Maehara N, Kusumoto M, Nabae T, Morisaki T, Katano M and Tanaka M: Establishment of a new human pancreatic cancer cell line, NOR-P1, with high angiogenic activity and metastatic potential. Cancer Lett. 155:153–161. 2000. View Article : Google Scholar : PubMed/NCBI

22 

Furukawa T, Duguid WP, Rosenberg L, Viallet J, Galloway DA and Tsao MS: Long-term culture and immortalization of epithelial cells from normal adult human pancreatic ducts transfected by the E6E7 gene of human papilloma virus 16. Am J Pathol. 148:1763–1770. 1996.PubMed/NCBI

23 

Zhang L, Mizumoto K, Sato N, Ogawa T, Kusumoto M, Niiyama H and Tanaka M: Quantitative determination of apoptotic death in cultured human pancreatic cancer cells by propidium iodide and digitonin. Cancer Lett. 142:129–137. 1999. View Article : Google Scholar : PubMed/NCBI

24 

Allen LF, Lefkowitz RJ, Caron MG and Cotecchia S: G-protein-coupled receptor genes as protooncogenes: Constitutively activating mutation of the alpha 1B-adrenergic receptor enhances mitogenesis and tumorigenicity. Proc Natl Acad Sci USA. 88:11354–11358. 1991. View Article : Google Scholar : PubMed/NCBI

25 

Knudsen LB, Hastrup S, Underwood CR, Wulff BS and Fleckner J: Functional importance of GLP-1 receptor species and expression levels in cell lines. Regul Pept. 175:21–29. 2012. View Article : Google Scholar : PubMed/NCBI

26 

Ge Y, Yang D, Dai A, Zhou C, Zhu Y and Wang MW: The putative signal peptide of glucagon-like peptide-1 receptor is not required for receptor synthesis but promotes receptor expression. Biosci Rep. 34:e001522014. View Article : Google Scholar : PubMed/NCBI

27 

Brom M, Joosten L, Oyen WJ, Gotthardt M and Boerman OC: Radiolabelled GLP-1 analogues for in vivo targeting of insulinomas. Contrast Media Mol Imaging. 7:160–166. 2012. View Article : Google Scholar : PubMed/NCBI

28 

Bodei L, Paganelli G and Mariani G: Receptor radionuclide therapy of tumors: A road from basic research to clinical applications. J Nucl Med. 47:375–377. 2006.PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Cases AI, Ohtsuka T, Kimura H, Zheng B, Shindo K, Oda Y, Mizumoto K, Nakamura M and Tanaka M: Significance of expression of glucagon-like peptide 1 receptor in pancreatic cancer. Oncol Rep 34: 1717-1725, 2015.
APA
Cases, A.I., Ohtsuka, T., Kimura, H., Zheng, B., Shindo, K., Oda, Y. ... Tanaka, M. (2015). Significance of expression of glucagon-like peptide 1 receptor in pancreatic cancer. Oncology Reports, 34, 1717-1725. https://doi.org/10.3892/or.2015.4138
MLA
Cases, A. I., Ohtsuka, T., Kimura, H., Zheng, B., Shindo, K., Oda, Y., Mizumoto, K., Nakamura, M., Tanaka, M."Significance of expression of glucagon-like peptide 1 receptor in pancreatic cancer". Oncology Reports 34.4 (2015): 1717-1725.
Chicago
Cases, A. I., Ohtsuka, T., Kimura, H., Zheng, B., Shindo, K., Oda, Y., Mizumoto, K., Nakamura, M., Tanaka, M."Significance of expression of glucagon-like peptide 1 receptor in pancreatic cancer". Oncology Reports 34, no. 4 (2015): 1717-1725. https://doi.org/10.3892/or.2015.4138
Copy and paste a formatted citation
x
Spandidos Publications style
Cases AI, Ohtsuka T, Kimura H, Zheng B, Shindo K, Oda Y, Mizumoto K, Nakamura M and Tanaka M: Significance of expression of glucagon-like peptide 1 receptor in pancreatic cancer. Oncol Rep 34: 1717-1725, 2015.
APA
Cases, A.I., Ohtsuka, T., Kimura, H., Zheng, B., Shindo, K., Oda, Y. ... Tanaka, M. (2015). Significance of expression of glucagon-like peptide 1 receptor in pancreatic cancer. Oncology Reports, 34, 1717-1725. https://doi.org/10.3892/or.2015.4138
MLA
Cases, A. I., Ohtsuka, T., Kimura, H., Zheng, B., Shindo, K., Oda, Y., Mizumoto, K., Nakamura, M., Tanaka, M."Significance of expression of glucagon-like peptide 1 receptor in pancreatic cancer". Oncology Reports 34.4 (2015): 1717-1725.
Chicago
Cases, A. I., Ohtsuka, T., Kimura, H., Zheng, B., Shindo, K., Oda, Y., Mizumoto, K., Nakamura, M., Tanaka, M."Significance of expression of glucagon-like peptide 1 receptor in pancreatic cancer". Oncology Reports 34, no. 4 (2015): 1717-1725. https://doi.org/10.3892/or.2015.4138
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