title: Hepatocellular Carcinoma-propagating Cells are Detectable by Side Population Analysis and Possess an Expression Profile Reflective of a Primitive Origin.
abstract: The recent identification of "Side Population" (SP) cells in a number of unrelated human cancers has renewed interests in the hypothesis of cancer stem cells. Here we isolated SP cells from HepG2 cells and 18 of the 21 fresh hepatocellular carcinoma (HCC) tissue samples. These SP cells have higher abilities of forming spheroids, invasion and migration. Tumors could generate only from SP, not non-SP (NSP), cells in a low dose of subcutaneous injection to the NOD/SCID mice (5 × 102cells/mouse). The mRNA microarray analysis of the SP vs. NSP cells isolated from HepG2 cells revealed that the SP cells express higher levels of pluripotency- and stem cell-associated transcription factors including Klf4, NF-Ya, SALL4 and HMGA2. Some of the known hepatobiliary progenitor/stem cell markers, such as Sox9 was also up-regulated. RT-qPCR analysis of the gene expression between SP cells and NSP cells isolated from both HepG2 cells and HCC tissue samples showed that most of the tested mRNAs' changes were in consistent with the microarray data, including the general progenitor/stem cells markers such as Klf4, NF-Ya, SALL4 and HMGA2, which were up-regulated in SP cells. Our data indicates that HCC cancer stem cells exist in HepG2 and HCC fresh tissue samples and can be isolated by SP assay.
authors.affiliation: Graduate School, Tianjin Medical University, No. 22, Qixiangtai Road, Tianjin 300070, China.|Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, Anhui Provincial Hospital, No. 17, Lujiang Road, Hefei 230001, China.
authors.forename: Honghai
authors.initials: H
authors.lastname: Xia
authors.affiliation: CAS Key Laboratory of Brain Function and Disease, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Chemistry for Life Sciences, School of Life Sciences, University of Science and Technology of China, No. 443, Huangshan Road, Hefei 230001, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cao
authors.affiliation: Central Laboratory of Medical research center, Anhui Provincial Hospital, No. 17, Lujiang Road, Hefei 230001, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.affiliation: Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, Anhui Provincial Hospital, No. 17, Lujiang Road, Hefei 230001, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Lv
authors.affiliation: Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, Anhui Provincial Hospital, No. 17, Lujiang Road, Hefei 230001, China.|Department of Hepatic Surgery, Anhui Provincial Hospital, No. 17, Lujiang Road, Hefei 230001, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Jia
authors.affiliation: Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, Anhui Provincial Hospital, No. 17, Lujiang Road, Hefei 230001, China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Ren
authors.affiliation: CAS Key Laboratory of Brain Function and Disease, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Chemistry for Life Sciences, School of Life Sciences, University of Science and Technology of China, No. 443, Huangshan Road, Hefei 230001, China.
authors.forename: Qingyu
authors.initials: Q
authors.lastname: Cheng
authors.affiliation: CAS Key Laboratory of Brain Function and Disease, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Chemistry for Life Sciences, School of Life Sciences, University of Science and Technology of China, No. 443, Huangshan Road, Hefei 230001, China.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Song
authors.affiliation: Graduate School, Tianjin Medical University, No. 22, Qixiangtai Road, Tianjin 300070, China.|Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, Anhui Provincial Hospital, No. 17, Lujiang Road, Hefei 230001, China.|Department of Hepatic Surgery, Anhui Provincial Hospital, No. 17, Lujiang Road, Hefei 230001, China.
authors.forename: Geliang
authors.initials: G
authors.lastname: Xu
mesh_terms: D000818:Animals; D023081:CCAAT-Binding Factor / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D025743:HMGA2 Protein / Q000235:genetics; D056945:Hep G2 Cells; D064593:Heterografts; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics; D008113:Liver Neoplasms / Q000473:pathology*; D051379:Mice; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000473:pathology*; D058985:Side-Population Cells / Q000473:pathology*; D014157:Transcription Factors / Q000235:genetics; D059467:Transcriptome
chemical_list: D023081:CCAAT-Binding Factor; D025743:HMGA2 Protein; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; C492061:NFYA protein, human; C472575:SALL4 protein, human; D014157:Transcription Factors