title: Identification of CD44+ cancer stem cells in human gastric cancer.
abstract: The cancer stem cell hypothesis suggests that tumors are initiated and maintained by cancer stem 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.
authors.forename: Wenji
authors.initials: W
authors.lastname: Chen
authors.forename: Xueping
authors.initials: X
authors.lastname: Zhang
authors.forename: Chiyuan
authors.initials: C
authors.lastname: Chu
authors.forename: Weunghong Leonard
authors.initials: WL
authors.lastname: Cheung
authors.forename: Lui
authors.initials: L
authors.lastname: Ng
authors.forename: Siaochi
authors.initials: S
authors.lastname: Lam
authors.forename: Ariel
authors.initials: A
authors.lastname: Chow
authors.forename: Tracy
authors.initials: T
authors.lastname: Lau
authors.forename: Minhu
authors.initials: M
authors.lastname: Chen
authors.forename: Yuyuan
authors.initials: Y
authors.lastname: Li
authors.forename: Yuqiang
authors.initials: Y
authors.lastname: Nie
authors.forename: Ben Chenyu
authors.initials: BC
authors.lastname: Wong
authors.forename: Roberta
authors.initials: R
authors.lastname: Pang
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D018960:Hyaluronan Receptors / Q000276:immunology*; D051379:Mice; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000276:immunology*; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D000964:Antimetabolites, Antineoplastic; D018960:Hyaluronan Receptors; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue; D005472:Fluorouracil