Identification of CD44+ cancer stem cells in human gastric cancer

Wenji Chen, Xueping Zhang, Chiyuan Chu, Weunghong Leonard Cheung, Lui Ng, Siaochi Lam, Ariel Chow, Tracy Lau, Minhu Chen, Yuyuan Li, Yuqiang Nie, Ben Chenyu Wong, Roberta Pang

Research output: Contribution to journalArticlepeer-review

50 Citations (Scopus)

Abstract

The cancer stem cell hypothesis suggests that tumors are initiated and maintained by a subset of cancer cells capable of self-renewal and differentiation into mature tumor cells. Recent studies have demonstrated the existence of cancer initiating cells in different solid tumors. In this study, we identified a subpopulation of CD44+ cells within the tumor of gastric cancer patients, which, upon treatment by chemotherapeutic agent 5-fluorouracil (5-FU), were markedly enriched. In vitro culture of isolated CD44+ subpopulation from gastric tumors by magnetic beads sorting led to formation of gastric spheroid colonies. These colonies retained CD44+ surface marker expression during culture, and were undifferentiated in nature. Subcutaneous injections of CD44+ gastric cancer cells conferred tumorigenicity in SCID mice. Moreover, implantation of CD44+ cells from these established tumors remained tumorigenic in successive passages. Using CD44+ cells isolated from the gastric cell lines AGS and SGC7901, similar results were obtained. Upon enrichment by 5-FU, CD44+ cells harbored increased ALDH expression as compared with CD44- cells. Our results demonstrated for the first time the existence of CD44+ cells within the tumors of gastric cancer patients that are endowed with stem cells properties, and also provide a plausible explanation for chemo-resistance frequently observed in gastric cancer patients. Such findings provide a basis for further studies on targeting this tumorigenic subpopulation for better treatment of gastric cancer patients.

Original languageEnglish
Pages (from-to)949-954
Number of pages6
JournalHepato-Gastroenterology
Volume60
Issue number124
DOIs
Publication statusPublished - Jun 2013
Externally publishedYes

Keywords

  • CD44
  • Cancer stem cell
  • Gastric cancer

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