Expression of GLP-1 Receptor and CD26 in Human Thyroid C-cells: The Association of Thyroid C-cell Tumorigenesis with Incretin-based Medicine

Overview

Journal Oncol Lett

Specialty Oncology

Date 2017 Apr 30

PMID 28454451

Citations 8

Authors

Yuejia Song

Min Zhou

Yang Cao

Jiping Qi

Jingshu Geng

Xiaomin Liu

Affiliations

Soon will be listed here.

Abstract

Recent reports have demonstrated that long-term and high dosage treatments with incretin-based medicine, such as hormone glucagon-like peptide-1 (GLP-1) may induce thyroid C-cell pathological changes in rodents, rather than in humans. Doubts regarding the tumorigenic potential of GLP-1 analogues in human thyroid C-cells remain. The present study aimed to determine the expression levels of GLP-1 receptor (GLP-1R) and cluster of differentiation 26 (CD26) in the C-cells of thyroid tissues from non-neoplastic, medullary carcinoma and hyperplasia subjects, and to explore the potential clinical significance. The following cases were analyzed: Medullary thyroid carcinoma (n=62, including 59 paraffin-embedded samples and 3 fresh frozen samples), C-cell hyperplasia (n=20, paraffin-embedded samples) and non-neoplastic thyroid tissue samples (n=7, paraffin-embedded samples). GLP-1R and CD26 expression was detected using immunohistochemical staining and western blotting. There were significant differences in the expression levels of the two markers between medullary thyroid carcinoma and C-cell hyperplasia, in addition to between medullary thyroid carcinoma and non-neoplastic thyroid tissue following immunohistochemical staining. Similar significant differences in the expression of GLP-1R and CD26 were detected using western blot analysis in the medullary thyroid carcinoma compared with non-neoplastic thyroid tissue sectioned from the aforementioned fresh frozen samples. There was a significant negative correlation between GLP-1R and CD26 expression. In addition, the present data indicated that GLP-1R expression was associated with the age of the patients with medullary thyroid carcinoma. These results suggested that GLP-1R and CD26 may be closely associated with the development of thyroid C-cell hyperplasia and medullary thyroid carcinoma, and indicated the importance of being aware of the side effects of incretin medicine.

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References

Cordero O, Salgado F, Nogueira M . On the origin of serum CD26 and its altered concentration in cancer patients. Cancer Immunol Immunother. 2009; 58(11):1723-47. PMC: 11031058. DOI: 10.1007/s00262-009-0728-1. View

Yazbeck R, Howarth G, Abbott C . Dipeptidyl peptidase inhibitors, an emerging drug class for inflammatory disease?. Trends Pharmacol Sci. 2009; 30(11):600-7. DOI: 10.1016/j.tips.2009.08.003. View

Aratake Y, Umeki K, Kiyoyama K, Hinoura Y, Sato S, Ohno A . Diagnostic utility of galectin-3 and CD26/DPPIV as preoperative diagnostic markers for thyroid nodules. Diagn Cytopathol. 2002; 26(6):366-72. DOI: 10.1002/dc.10111. View

Wesley U, Albino A, Tiwari S, Houghton A . A role for dipeptidyl peptidase IV in suppressing the malignant phenotype of melanocytic cells. J Exp Med. 1999; 190(3):311-22. PMC: 2195594. DOI: 10.1084/jem.190.3.311. View

Mentlein R . Dipeptidyl-peptidase IV (CD26)--role in the inactivation of regulatory peptides. Regul Pept. 1999; 85(1):9-24. DOI: 10.1016/s0167-0115(99)00089-0. View

Parks M, Rosebraugh C . Weighing risks and benefits of liraglutide--the FDA's review of a new antidiabetic therapy. N Engl J Med. 2010; 362(9):774-7. DOI: 10.1056/NEJMp1001578. View

Vara E, Arias-Diaz J, Garcia C, Balibrea J, Blazquez E . Glucagon-like peptide-1(7-36) amide stimulates surfactant secretion in human type II pneumocytes. Am J Respir Crit Care Med. 2001; 163(4):840-6. DOI: 10.1164/ajrccm.163.4.9912132. View

Knudsen L, Madsen L, Andersen S, Almholt K, DE Boer A, Drucker D . Glucagon-like Peptide-1 receptor agonists activate rodent thyroid C-cells causing calcitonin release and C-cell proliferation. Endocrinology. 2010; 151(4):1473-86. DOI: 10.1210/en.2009-1272. View

Peters A . Incretin-based therapies: review of current clinical trial data. Am J Med. 2010; 123(3 Suppl):S28-37. DOI: 10.1016/j.amjmed.2009.12.007. View

10.

Sato T, Yamochi T, Yamochi T, Aytac U, Ohnuma K, McKee K . CD26 regulates p38 mitogen-activated protein kinase-dependent phosphorylation of integrin beta1, adhesion to extracellular matrix, and tumorigenicity of T-anaplastic large cell lymphoma Karpas 299. Cancer Res. 2005; 65(15):6950-6. DOI: 10.1158/0008-5472.CAN-05-0647. View

11.

Lima M, Gontijo V, Schmitt F . CD26 (Dipeptidyl Aminopeptidase IV) Expression in Normal and Diseased Human Thyroid Glands. Endocr Pathol. 2002; 9(1):43-52. DOI: 10.1007/BF02739951. View

12.

Mayo K, Miller L, Bataille D, Dalle S, Goke B, Thorens B . International Union of Pharmacology. XXXV. The glucagon receptor family. Pharmacol Rev. 2003; 55(1):167-94. DOI: 10.1124/pr.55.1.6. View

13.

Baggio L, Drucker D . Biology of incretins: GLP-1 and GIP. Gastroenterology. 2007; 132(6):2131-57. DOI: 10.1053/j.gastro.2007.03.054. View

14.

Satoh F, Beak S, Small C, Falzon M, Ghatei M, Bloom S . Characterization of human and rat glucagon-like peptide-1 receptors in the neurointermediate lobe: lack of coupling to either stimulation or inhibition of adenylyl cyclase. Endocrinology. 2000; 141(4):1301-9. DOI: 10.1210/endo.141.4.7420. View

15.

Cao Y, Liu X . Should we still be concerned about the potential side effects of glucagon-like peptide-1 receptor agonists on thyroid C cells?. Endocrine. 2014; 48(1):47-52. DOI: 10.1007/s12020-014-0354-3. View

16.

Wei Y, Mojsov S . Tissue-specific expression of the human receptor for glucagon-like peptide-I: brain, heart and pancreatic forms have the same deduced amino acid sequences. FEBS Lett. 1995; 358(3):219-24. DOI: 10.1016/0014-5793(94)01430-9. View

17.

Hildebrandt M, Rose M, Ruter J, Salama A, Monnikes H, Klapp B . Dipeptidyl peptidase IV (DP IV, CD26) in patients with inflammatory bowel disease. Scand J Gastroenterol. 2001; 36(10):1067-72. DOI: 10.1080/003655201750422675. View

18.

Vangoitsenhoven R, Mathieu C, Van der Schueren B . GLP1 and cancer: friend or foe?. Endocr Relat Cancer. 2012; 19(5):F77-88. DOI: 10.1530/ERC-12-0111. View

19.

Williams-Herman D, Engel S, Round E, Johnson J, Golm G, Guo H . Safety and tolerability of sitagliptin in clinical studies: a pooled analysis of data from 10,246 patients with type 2 diabetes. BMC Endocr Disord. 2010; 10:7. PMC: 3161395. DOI: 10.1186/1472-6823-10-7. View

20.

Waser B, Beetschen K, Pellegata N, Reubi J . Incretin receptors in non-neoplastic and neoplastic thyroid C cells in rodents and humans: relevance for incretin-based diabetes therapy. Neuroendocrinology. 2011; 94(4):291-301. DOI: 10.1159/000330447. View