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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2008-7-22
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1541-7786
pubmed:author
pubmed:issnType
Print
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1146-53
pubmed:meshHeading
pubmed-meshheading:18644979-Aldehyde Dehydrogenase, pubmed-meshheading:18644979-Animals, pubmed-meshheading:18644979-Antigens, CD, pubmed-meshheading:18644979-Blotting, Western, pubmed-meshheading:18644979-Carcinoma, Hepatocellular, pubmed-meshheading:18644979-Cell Line, Tumor, pubmed-meshheading:18644979-Electrophoresis, Gel, Two-Dimensional, pubmed-meshheading:18644979-Flow Cytometry, pubmed-meshheading:18644979-Glycoproteins, pubmed-meshheading:18644979-Isoenzymes, pubmed-meshheading:18644979-Liver Neoplasms, pubmed-meshheading:18644979-Mice, pubmed-meshheading:18644979-Mice, SCID, pubmed-meshheading:18644979-Neoplasm Proteins, pubmed-meshheading:18644979-Neoplastic Stem Cells, pubmed-meshheading:18644979-Peptides, pubmed-meshheading:18644979-Polymerase Chain Reaction, pubmed-meshheading:18644979-Proteomics
pubmed:year
2008
pubmed:articleTitle
Aldehyde dehydrogenase discriminates the CD133 liver cancer stem cell populations.
pubmed:affiliation
Department of Clinical Oncology, The University of Hong Kong, Pokfulam, Hong Kong, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't