TY - JOUR
T1 - Identification of CD44+ cancer stem cells in human gastric cancer
AU - Chen, Wenji
AU - Zhang, Xueping
AU - Chu, Chiyuan
AU - Cheung, Weunghong Leonard
AU - Ng, Lui
AU - Lam, Siaochi
AU - Chow, Ariel
AU - Lau, Tracy
AU - Chen, Minhu
AU - Li, Yuyuan
AU - Nie, Yuqiang
AU - Wong, Ben Chenyu
AU - Pang, Roberta
PY - 2013/6
Y1 - 2013/6
N2 - 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.
AB - 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.
KW - CD44
KW - Cancer stem cell
KW - Gastric cancer
UR - http://www.scopus.com/inward/record.url?scp=84879584481&partnerID=8YFLogxK
U2 - 10.5754/hge12881
DO - 10.5754/hge12881
M3 - Article
C2 - 23478146
AN - SCOPUS:84879584481
SN - 0172-6390
VL - 60
SP - 949
EP - 954
JO - Hepato-Gastroenterology
JF - Hepato-Gastroenterology
IS - 124
ER -