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Article: Aldehyde dehydrogenase discriminates the CD133 liver cancer stem cell populations

TitleAldehyde dehydrogenase discriminates the CD133 liver cancer stem cell populations
Authors
Issue Date2008
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://mcr.aacrjournals.org/
Citation
Molecular Cancer Research, 2008, v. 6 n. 7, p. 1146-1153 How to Cite?
AbstractRecent 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. Copyright © 2008 American Association for Cancer Research.
Persistent Identifierhttp://hdl.handle.net/10722/58600
ISSN
2015 Impact Factor: 4.51
2015 SCImago Journal Rankings: 2.534
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorMa, Sen_HK
dc.contributor.authorKwok, WCen_HK
dc.contributor.authorLee, TKWen_HK
dc.contributor.authorKwan, HTen_HK
dc.contributor.authorWo, JYHen_HK
dc.contributor.authorZheng, BJen_HK
dc.contributor.authorGuan, XYen_HK
dc.date.accessioned2010-05-31T03:33:16Z-
dc.date.available2010-05-31T03:33:16Z-
dc.date.issued2008en_HK
dc.identifier.citationMolecular Cancer Research, 2008, v. 6 n. 7, p. 1146-1153en_HK
dc.identifier.issn1541-7786en_HK
dc.identifier.urihttp://hdl.handle.net/10722/58600-
dc.description.abstractRecent 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. Copyright © 2008 American Association for Cancer Research.en_HK
dc.languageengen_HK
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://mcr.aacrjournals.org/en_HK
dc.relation.ispartofMolecular Cancer Researchen_HK
dc.subject.meshAldehyde Dehydrogenase - metabolismen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshAntigens, CD - metabolismen_HK
dc.subject.meshBlotting, Westernen_HK
dc.subject.meshCarcinoma, Hepatocellular - enzymology - pathologyen_HK
dc.subject.meshCell Line, Tumoren_HK
dc.subject.meshElectrophoresis, Gel, Two-Dimensionalen_HK
dc.subject.meshFlow Cytometryen_HK
dc.subject.meshGlycoproteins - metabolismen_HK
dc.subject.meshIsoenzymes - metabolismen_HK
dc.subject.meshLiver Neoplasms - enzymology - pathologyen_HK
dc.subject.meshMiceen_HK
dc.subject.meshMice, SCIDen_HK
dc.subject.meshNeoplasm Proteins - metabolismen_HK
dc.subject.meshNeoplastic Stem Cells - enzymology - pathologyen_HK
dc.subject.meshPeptides - metabolismen_HK
dc.subject.meshPolymerase Chain Reactionen_HK
dc.subject.meshProteomicsen_HK
dc.titleAldehyde dehydrogenase discriminates the CD133 liver cancer stem cell populationsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1541-7786&volume=6&spage=1146&epage=1153&date=2008&atitle=Aldehyde+dehydrogenase+discriminates+the+CD133+liver+cancer+stem+cell+populationsen_HK
dc.identifier.emailMa, S:sma@pathology.hku.hken_HK
dc.identifier.emailLee, TKW:tkwlee@hkucc.hku.hken_HK
dc.identifier.emailZheng, BJ:bzheng@hkucc.hku.hken_HK
dc.identifier.emailGuan, XY:xyguan@hkucc.hku.hken_HK
dc.identifier.authorityMa, S=rp00506en_HK
dc.identifier.authorityLee, TKW=rp00447en_HK
dc.identifier.authorityZheng, BJ=rp00353en_HK
dc.identifier.authorityGuan, XY=rp00454en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1158/1541-7786.MCR-08-0035en_HK
dc.identifier.pmid18644979en_HK
dc.identifier.scopuseid_2-s2.0-51649119918en_HK
dc.identifier.hkuros144430en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-51649119918&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume6en_HK
dc.identifier.issue7en_HK
dc.identifier.spage1146en_HK
dc.identifier.epage1153en_HK
dc.identifier.isiWOS:000257895900007-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridMa, S=16444895800en_HK
dc.identifier.scopusauthoridKwok, WC=24171150800en_HK
dc.identifier.scopusauthoridLee, TKW=7501439435en_HK
dc.identifier.scopusauthoridKwan, HT=25223083100en_HK
dc.identifier.scopusauthoridWo, JYH=7003466728en_HK
dc.identifier.scopusauthoridZheng, BJ=7201780588en_HK
dc.identifier.scopusauthoridGuan, XY=7201463221en_HK

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