Aldehyde Dehydrogenase Discriminates the CD133 Liver Cancer Stem Cell Populations
Stephanie Ma,Kwok Wah Chan,Terence Kin Wah Lee,Kwan Ho Tang,Jana Yim-Hung Wo,Bo-Jian Zheng,Xin Yuan Guan +6 more
TLDR
Comparing protein profiles between CD133+ and CD133− subpopulations isolated from Huh7 and PLC8024 and identifying aldehyde dehydrogenase 1A1 as one of the proteins that are preferentially expressed in theCD133+ subfraction reveals the existence of a hierarchical organization in HCC bearing tumorigenic potential in the order of CD133+.Abstract:
Recent efforts in our study of cancer stem cells (CSC) in hepatocellular carcinoma (HCC) have led to the identification of CD133 as a prominent HCC CSC marker. Findings were based on experiments done on cell lines and xenograft tumors where expression of CD133 was detected at levels as high as 65%. Based on the CSC theory, CSCs are believed to represent only a minority number of the tumor mass. This is indicative that our previously characterized CD133+ HCC CSC population is still heterogeneous, consisting of perhaps subsets of cells with differing tumorigenic potential. We hypothesized that it is possible to further enrich the CSC population by means of additional differentially expressed markers. Using a two-dimensional PAGE approach, we compared protein profiles between CD133+ and CD133− subpopulations isolated from Huh7 and PLC8024 and identified aldehyde dehydrogenase 1A1 as one of the proteins that are preferentially expressed in the CD133+ subfraction. Analysis of the expression of several different ALDH isoforms and ALDH enzymatic activity in liver cell lines found ALDH to be positively correlated with CD133 expression. Dual-color flow cytometry analysis found the majority of ALDH+ to be CD133+, yet not all CD133+ HCC cells were ALDH+. Subsequent studies on purified subpopulations found CD133+ALDH+ cells to be significantly more tumorigenic than their CD133−ALDH+ or CD133−ALDH− counterparts, both in vitro and in vivo. These data, combined with those from our previous work, reveal the existence of a hierarchical organization in HCC bearing tumorigenic potential in the order of CD133+ALDH+ > CD133+ALDH− > CD133−ALDH−. ALDH, expressed along CD133, can more specifically characterize the tumorigenic liver CSC population. (Mol Cancer Res 2008;6(7):1146–53)read more
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Tackling the cancer stem cells — what challenges do they pose?
TL;DR: The signalling pathways that create cancer stem cells, cell-intrinsic mechanisms that could be exploited for selective elimination or induction of their differentiation, and the role of the tumour microenvironment in sustaining them are discussed.
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Mechanisms of chemoresistance in cancer stem cells
TL;DR: By understanding how tumor-initiating cells such as CSCs escape chemotherapy, more informed approaches to treating cancer will develop and may improve clinical outcomes for cancer patients, this review describes a number of mechanisms of chemoresistance in cancer stem cells.
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Aldehyde dehydrogenase in combination with CD133 defines angiogenic ovarian cancer stem cells that portend poor patient survival.
Ines A. Silva,Shoumei Bai,Karen McLean,Kun Yang,Kent A. Griffith,Dafydd G. Thomas,Christophe Ginestier,Carolyn Johnston,Angela Kueck,R. Kevin Reynolds,Max S. Wicha,Ronald J. Buckanovich +11 more
TL;DR: ALDH and CD133 are defined as a functionally significant set of markers to identify ovarian CSCs and the presence of ALDH(+)CD133(+) cells in debulked primary tumor specimens correlated with reduced disease-free and overall survival in ovarian cancer patients.
Journal ArticleDOI
Aldehyde dehydrogenase: Its role as a cancer stem cell marker comes down to the specific isoform
TL;DR: The suggested roles of ALDH in CSC biology and the immunohistological studies testing the potential application of AL DH isoforms as novel cancer prognostic indicators are reviewed.
Journal ArticleDOI
Aldehyde dehydrogenase 1 is a putative marker for cancer stem cells in head and neck squamous cancer.
Yu Chih Chen,Yi Wei Chen,Yi Wei Chen,Han Shui Hsu,Han Shui Hsu,Ling Ming Tseng,Ling Ming Tseng,Pin I. Huang,Pin I. Huang,Kai Hsi Lu,Dow Tien Chen,Lung Kuo Tai,Lung Kuo Tai,Ming Chi Yung,Shih Ching Chang,Shih Ching Chang,Hung Hai Ku,Shih Hwa Chiou,Shih Hwa Chiou,Wen Liang Lo,Wen Liang Lo +20 more
TL;DR: It is likely that ALDH1 is a specific marker for the cancer stem-like cells of HNSCC, and the treatment effect of chemoradiotherapy for AL DH1+ could be improved by Snail siRNA.
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