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PMID: 19415765 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Identification of gastric cancer stem cells using the cell surface marker CD44.

Stem cells (Dayton, Ohio) ·Vol. 27 ·No. 5 ·2009-05-00 ·Pages 1006-20

Takaishi S, Okumura T, Tu S, Wang SS, Shibata W, Vigneshwaran R, Gordon SA, Shimada Y, Wang TC

Abstract

Cancer stem cells (CSCs) have been defined as a unique subpopulation in tumors that possess the ability to initiate tumor growth and sustain tumor self-renewal. Although the evidence has been provided to support the existence of CSCs in various solid tumors, the identity of gastric CSCs has not been reported. In this study, we have identified gastric cancer-initiating cells from a panel of human gastric cancer cell lines using cell surface marker CD44. Among six gastric cancer cell lines, three lines MKN-45, MKN-74, and NCI-N87 had a sizeable subpopulation of CD44(+) cells, and these cells showed spheroid colony formation in serum-free media in vitro as well as tumorigenic ability when injected into stomach and skin of severe combined immunodeficient (SCID) mice in vivo. The CD44(+) gastric cancer cells showed the stem cell properties of self-renewal and the ability to form differentiated progeny and gave rise to CD44(-) cells. CD44 knockdown by short hairpin RNA resulted in much reduced spheroid colony formation and smaller tumor production in SCID mice, and the CD44(-) populations had significantly reduced tumorigenic ability in vitro and in vivo. Other potential CSC markers, such as CD24, CD133, CD166, stage-specific embryonic antigen-1 (SSEA-1), and SSEA-4, or sorting for side population did not show any correlation with tumorigenicity in vitro or in vivo. The CD44(+) gastric cancer cells showed increased resistance for chemotherapy- or radiation-induced cell death. These results support the existence of gastric CSCs and may provide novel approaches to the diagnosis and treatment of gastric cancer.

MeSH Terms
Animals Biomarkers, Tumor/metabolism Cell Line, Tumor Culture Media, Serum-Free Disease Models, Animal Drug Resistance, Neoplasm Humans Hyaluronan Receptors/metabolism Mice Mice, SCID Neoplastic Stem Cells/metabolism,pathology RNA, Small Interfering/metabolism Radiation Tolerance Spheroids, Cellular/pathology Stomach Neoplasms/metabolism,pathology
Chemicals
Biomarkers, Tumor Culture Media, Serum-Free Hyaluronan Receptors RNA, Small Interfering
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Takaishi Shigeo
Division of Digestive and Liver Disease, Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
Okumura Tomoyuki
Tu Shuiping
Wang Sophie S W
Shibata Wataru
Vigneshwaran Ramanathan
Gordon Shanisha A K
Shimada Yutaka
Wang Timothy C
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Article Info
Journal
Stem cells (Dayton, Ohio)
Abbr.
Stem Cells
ISSN
1549-4918
DOI
10.1002/stem.30
Published
2009-05-00
Pages
1006-20
Language
English
Region
United States
NLM ID
9304532
PMCID
PMC2746367
Subset
IM
Grants
NCI NIH HHS · R01 CA093405 · United States
NCI NIH HHS · R01 CA120979 · United States
NCI NIH HHS · R01 CA120979-02 · United States
External Links
PubMed source DOI: 10.1002/stem.30 PMC Full Text View journal details
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