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PMID: 21480217 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Expression of aldehyde dehydrogenase and CD133 defines ovarian cancer stem cells.

International journal of cancer ·Vol. 130 ·No. 1 ·2012-01-01 ·Pages 29-39

Kryczek I, Liu S, Roh M, Vatan L, Szeliga W, Wei S, Banerjee M, Mao Y, Kotarski J, Wicha MS, Liu R, Zou W

Abstract

Identification of cancer stem cells is crucial for advancing cancer biology and therapy. Several markers including CD24, CD44, CD117, CD133, the G subfamily of ATP-binding cassette transporters (ABCG), epithelial specific antigen (ESA) and aldehyde dehydrogenase (ALDH) are used to identify and investigate human epithelial cancer stem cells in the literature. We have now systemically analyzed and compared the expression of these markers in fresh ovarian epithelial carcinomas. Although the expression levels of these markers were unexpectedly variable and partially overlapping in fresh ovarian cancer cells from different donors, we reliably detected important levels of CD133 and ALDH in the majority of fresh ovarian cancer. Furthermore, most of these stem cell markers including CD133 and ALDH were gradually lost following in vitro passage of primary tumor cells. However, the expression of ALDH and CD133, but not CD24, CD44 and CD117, could be partially rescued by the in vitro serum-free and sphere cultures and by the in vivo passage in the immune-deficient xenografts. ALDH+ and CD133+ cells formed three-dimensional spheres more efficiently than their negative counterparts. These sphere-forming cells expressed high levels of stem cell core gene transcripts and could be expanded and form additional spheres in long-term culture. ALDH+ , CD133+ and ALDH+ CD133+ cells from fresh tumors developed larger tumors more rapidly than their negative counterparts. This property was preserved in the xenografted tumors. Altogether, the data suggest that ALDH+ and CD133+ cells are enriched with ovarian cancer-initiating (stem) cells and that ALDH and CD133 may be widely used as reliable markers to investigate ovarian cancer stem cell biology.

MeSH Terms
AC133 Antigen ATP Binding Cassette Transporter, Subfamily D, Member 1 ATP-Binding Cassette Transporters/genetics,metabolism Animals Antigens, CD/genetics,metabolism Carcinoma, Ovarian Epithelial Cell Proliferation Female Flow Cytometry Fluorescent Antibody Technique Glycoproteins/genetics,metabolism Humans Mice Mice, Inbred NOD Mice, SCID Neoplasms, Glandular and Epithelial/genetics,metabolism,pathology Neoplastic Stem Cells/metabolism,pathology Ovarian Neoplasms/genetics,metabolism,pathology Peptides/genetics,metabolism Real-Time Polymerase Chain Reaction Tumor Cells, Cultured
Chemicals
ABCD1 protein, human AC133 Antigen ATP Binding Cassette Transporter, Subfamily D, Member 1 ATP-Binding Cassette Transporters Antigens, CD Glycoproteins PROM1 protein, human Peptides Prom1 protein, mouse
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Kryczek Ilona
Department of Surgery, University of Michigan, Ann Arbor, MI 48109-0669, USA.
Liu Suling
Roh Michael
Vatan Linhua
Szeliga Wojciech
Wei Shuang
Banerjee Mousumi
Mao Yujun
Kotarski Jan
Wicha Max S
Liu Rebecca
Zou Weiping
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Article Info
Journal
International journal of cancer
Abbr.
Int J Cancer
ISSN
1097-0215
DOI
10.1002/ijc.25967
Published
2012-01-01
Epub
2011-00-08
Pages
29-39
Language
English
Region
United States
NLM ID
0042124
PMCID
PMC3164893
Subset
IM
Grants
NCI NIH HHS · CA099985 · United States
NCI NIH HHS · CA156685 · United States
NCI NIH HHS · P30 CA046592 · United States
NCI NIH HHS · 5P30 CA46592 · United States
NCI NIH HHS · R01 CA156685-01 · United States
NCI NIH HHS · R01 CA152470 · United States
NCI NIH HHS · R01 CA156685 · United States
NCI NIH HHS · CA123088 · United States
NCI NIH HHS · R01 CA099985 · United States
NCI NIH HHS · R01 CA099985-01A2 · United States
NCI NIH HHS · R01 CA123088 · United States
External Links
PubMed source DOI: 10.1002/ijc.25967 PMC Full Text View journal details
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