Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 7, 2015; 21(13): 3876-3887
Published online Apr 7, 2015. doi: 10.3748/wjg.v21.i13.3876
Fucosylation is a common glycosylation type in pancreatic cancer stem cell-like phenotypes
Naoko Terao, Shinji Takamatsu, Tomomi Minehira, Tomoaki Sobajima, Kotarosumitomo Nakayama, Yoshihiro Kamada, Eiji Miyoshi
Naoko Terao, Shinji Takamatsu, Tomomi Minehira, Tomoaki Sobajima, Kotarosumitomo Nakayama, Yoshihiro Kamada, Eiji Miyoshi, Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Suita 565-0871, Japan
Author contributions: Miyoshi E designed the research; Terao N, Takamatsu S, Minehira T, Sobajima T and Nakayama K performed the research; Takamatsu S and Kamada Y analyzed the data; Terao N, Kamada Y and Miyoshi E wrote the paper.
Supported by Grant-in-Aid for Scientific Research (A; No. 21249038) from the Japan Society for the Promotion of Science, and partially supported as a research program of the Project for Development of Innovative Research on Cancer Therapeutics (P-Direct), Ministry of Education, Culture, Sports, Science and Technology of Japan.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Eiji Miyoshi, MD, Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, 1-7 Yamada-oka, Suita 565-0871, Japan. emiyoshi@sahs.med.osaka-u.ac.jp
Telephone: +81-6-68792590 Fax: +81-6-68792590
Received: August 3, 2014
Peer-review started: August 4, 2014
First decision: August 27, 2014
Revised: September 21, 2014
Accepted: November 30, 2014
Article in press: December 1, 2014
Published online: April 7, 2015
Processing time: 247 Days and 2.1 Hours
Abstract

AIM: To evaluate/isolate cancer stem cells (CSCs) from tissue or cell lines according to various definitions and cell surface markers.

METHODS: Lectin microarray analysis was conducted on CSC-like fractions of the human pancreatic cancer cell line Panc1 by establishing anti-cancer drug-resistant cells. Changes in glycan structure of CSC-like cells were also investigated in sphere-forming cells as well as in CSC fractions obtained from overexpression of CD24 and CD44.

RESULTS: Several types of fucosylation were increased under these conditions, and the expression of fucosylation regulatory genes such as fucosyltransferases, GDP-fucose synthetic enzymes, and GDP-fucose transporters were dramatically enhanced in CSC-like cells. These changes were significant in gemcitabine-resistant cells and sphere cells of a human pancreatic cancer cell line, Panc1. However, downregulation of cellular fucosylation by knockdown of the GDP-fucose transporter did not alter gemcitabine resistance, indicating that increased cellular fucosylation is a result of CSC-like transformation.

CONCLUSION: Fucosylation might be a biomarker of CSC-like cells in pancreatic cancer.

Keywords: Anti-cancer drug resistance; Cancer stem cells; Fucosylation; Glycosylation; Pancreatic cancer; Sphere formation

Core tip: Fucosylation is one of the most important glycosylation events involved in cancer and inflammation. In the present study, we investigated oligosaccharide modifications in pancreatic cancer cancer stem cell (CSC)-like cells. Using several models of CSC-like cells, we found that fucosylation is a common type of glycosylation change in pancreatic cancer CSC-like cells. CSCs are known to be preferentially resistant to many current therapies, including various chemotherapeutic agents and radiation treatment. Our present study suggests that the identification of fucosylated glycoproteins derived from pancreatic cancer cells could lead to novel biomarker development for anticancer drug resistance.