Expression of aldehyde dehydrogenase and CD133 defines ovarian cancer stem cells
Open Access
- 3 February 2011
- journal article
- research article
- Published by Wiley in International Journal of Cancer
- Vol. 130 (1), 29-39
- https://doi.org/10.1002/ijc.25967
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.Keywords
This publication has 42 references indexed in Scilit:
- Targeting Aldehyde Dehydrogenase Cancer Stem Cells in Ovarian CancerMolecular Cancer Therapeutics, 2010
- Inhibitory B7-family molecules in the tumour microenvironmentNature Reviews Immunology, 2008
- BRCA1 regulates human mammary stem/progenitor cell fateProceedings of the National Academy of Sciences of the United States of America, 2008
- Mutations in the EGFR kinase domain mediate STAT3 activation via IL-6 production in human lung adenocarcinomasJCI Insight, 2007
- Cutting Edge: Th17 and Regulatory T Cell Dynamics and the Regulation by IL-2 in the Tumor MicroenvironmentThe Journal of Immunology, 2007
- Immunosuppressive networks in the tumour environment and their therapeutic relevanceNature Reviews Cancer, 2005
- Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survivalNature Medicine, 2004
- Stem cells in normal breast development and breast cancerCell Proliferation, 2003
- Blockade of B7-H1 improves myeloid dendritic cell–mediated antitumor immunityNature Medicine, 2003
- Stem cells, cancer, and cancer stem cellsNature, 2001