Research Report
Copyright ©2014 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 14, 2014; 20(34): 12171-12181
Published online Sep 14, 2014. doi: 10.3748/wjg.v20.i34.12171
Inhibition of KL-6/MUC1 glycosylation limits aggressive progression of pancreatic cancer
Huan-Li Xu, Xin Zhao, Ke-Ming Zhang, Wei Tang, Norihiro Kokudo
Huan-Li Xu, Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China
Xin Zhao, Ke-Ming Zhang, Department of Hepatobiliary Surgery, 302 Hospital of Chinese People’s Liberation Army, Beijing 100039, China
Wei Tang, Norihiro Kokudo, Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo 113-8654, Japan
Author contributions: Xu HL and Zhao X performed the experiments; Xu HL, Zhang KM and Tang W designed the study and wrote the manuscript; Zhang KM, Tang W and Kokudo N collected all the human material and provided financial support for this work.
Supported by Grants from the National Natural Science Foundation of China, No. 81302906; Beijing Natural Science Foundation, No. 7144190; and New Teacher Fund for Doctor Stations of Ministry of Education of China, No. 20131107120019
Correspondence to: Ke-Ming Zhang, MD, Department of Hepatobiliary Surgery, 302 Hospital of Chinese People’s Liberation Army, 100, The 4th Ring Road, Beijing 100039, China. zhangkeming302@sina.cn
Telephone: +86-10-83911837 Fax: +86-10-83911520
Received: March 24, 2014
Revised: May 23, 2014
Accepted: June 21, 2014
Published online: September 14, 2014
Abstract

AIM: To evaluate the significance of KL-6/MUC1 (a type of MUC1) glycosylation in pancreatic cancer progression.

METHODS: KL-6/MUC1 expression was detected by immunohistochemistry in 48 patients with pancreatic duct cell carcinoma. The N-/O-glycosylation inhibitors (tunicamycin and benzyl-N-acetyl-α-galactosaminide) were then used to interfere with KL-6/MUC1 glycosylation in two pancreatic carcinoma cell lines, and the effects on KL-6/MUC1 expression, and cell adhesion and invasion were determined. In addition, protein expression of epithelial-mesenchymal transition markers, E-cadherin and vimentin, were evaluated in cells after treatment with glycosylation inhibitors.

RESULTS: Overexpression of KL-6/MUC1 was found in all pancreatic cancer tissues, but not in the surrounding normal pancreatic tissues. The expression profile of KL-6/MUC1 was significantly decreased after treatment with the inhibitors. The adhesion and invasive ability of cancer cells were significantly decreased after drug treatment, and increased E-cadherin and decreased vimentin expression were found.

CONCLUSION: KL-6/MUC1 glycosylation is involved in pancreatic cancer metastasis and invasion. Therapeutic strategies which target this may help control the aggressive behavior of pancreatic cancer cells.

Keywords: Benzyl-N-acetyl-α-galactosaminide, Glycosylation, KL-6/MUC1, Pancreatic carcinoma, Tunicamycin

Core tip: Aberrant glycosylation of MUC1 is associated with aggressive tumor behavior in many carcinomas. This study evaluated the significance of KL-6/MUC1 glycosylation in pancreatic cancer progression. The results indicate the important involvement of KL-6/MUC1 glycosylation in pancreatic cancer metastasis and invasion, which may be related to the epithelial-mesenchymal transition process. Therapeutic strategies which target glycosylation of KL-6/MUC1 may be useful for controlling the aggressive behavior of pancreatic cancer cells.