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World J Gastroenterol. Jan 7, 2015; 21(1): 112-123
Published online Jan 7, 2015. doi: 10.3748/wjg.v21.i1.112
Stem cells in gastric cancer
Yue Zhao, Fei Feng, Yong-Ning Zhou
Yue Zhao, Yong-Ning Zhou, Division of Gastroenterology and Hepatology, the First Hospital of Lanzhou University, Key Laboratory for Gastrointestinal Disease of Gansu Province, Lanzhou 730000, Gansu Province, China
Fei Feng, Division of Ultrasonography, the First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
Author contributions: Zhao Y and Zhou YN designed the study; Zhao Y, Feng F and Zhou YN wrote the manuscript.
Supported by Fundamental Research Funds for the Central Universities lzujbky-2013-221, China’s National Science and Technology Program for Public Wellbeing Grant No. 2012GS620101 and Major Science and Technology Projects of Gansu Province Grant No. 1102FKDA006
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: Yong-Ning Zhou, MD, Division of Gastroenterology and Hepatology, the First Hospital of Lanzhou University, Key Laboratory for Gastrointestinal Disease of Gansu Province, 1 Donggaung West Road, Lanzhou 730000, Gansu Province, China. yongningzhou@163.com
Telephone: +86-931-8356238 Fax: +86-931-8619797
Received: August 12, 2014
Peer-review started: August 12, 2014
First decision: August 27, 2014
Revised: September 19, 2014
Accepted: October 20, 2014
Article in press: October 21, 2014
Published online: January 7, 2015
Processing time: 147 Days and 21 Hours
Abstract

Gastric cancer (GC) is one of the leading causes of cancer-related mortality worldwide. Cancer stem cells (CSCs), which were first identified in acute myeloid leukemia and subsequently in a large array of solid tumors, play important roles in cancer initiation, dissemination and recurrence. CSCs are often transformed tissue-specific stem cells or de-differentiated transit amplifying progenitor cells. Several populations of multipotent gastric stem cells (GSCs) that reside in the stomach have been determined to regulate physiological tissue renewal and injury repair. These populations include the Villin+ and Lgr5+ GSCs in the antrum, the Troy+ chief cells in the corpus, and the Sox2+ GSCs that are found in both the antrum and the corpus. The disruption of tumor suppressors in Villin+ or Lgr5+ GSCs leads to GC in mouse models. In addition to residing GSCs, bone marrow-derived cells can initiate GC in a mouse model of chronic Helicobacter infection. Furthermore, expression of the cell surface markers CD133 or CD44 defines gastric CSCs in mouse models and in human primary GC tissues and cell lines. Targeted elimination of CSCs effectively reduces tumor size and grade in mouse models. In summary, the recent identification of normal GSCs and gastric CSCs has greatly improved our understanding of the molecular and cellular etiology of GC and will aid in the development of effective therapies to treat patients.

Keywords: Cancer stem cells; Gastric cancer; Lgr5; Villin; Troy; Sox2; CD133; CD44; E-cadherin

Core tip: Cancer stem cells (CSCs) play important roles in cancer initiation, dissemination and recurrence. The recent identification of normal gastric stem cells and gastric CSCs has greatly improved our understanding of the molecular and cellular etiology of gastric cancer and will help with the design of effective treatments. In this article, we review the literature on the recent progress in the identification and characterization of normal gastric stem cells and gastric CSCs and discuss the implications for the treatment of gastric cancer.