title: Differential proteomic analysis of cancer stem cell properties in hepatocellular carcinomas by isobaric tag labeling and mass spectrometry.
abstract: Malignant tumors are relatively resistant to treatment due to their heterogeneous nature, drug resistance, and tendency for metastasis. Recent studies suggest that a subpopulation of cancer cells is responsible for the malignant outcomes. These cells are considered as cancer stem cells (CSC). Although a number of molecules have been identified in different cancer cells as markers for cancer stem cells, no promising markers are currently available for hepatocellular carcinoma cells. In this study, two clones of Hep3B cell lines were functionally characterized as control or CSC-like cells, based on properties including spheroid formation, drug resistance, and tumor initiation. Furthermore, their protein expression profiles were investigated by isobaric tags for relative and absolute quantitation (iTRAQ), and a total of 1,127 proteins were identified and quantified from the combined fractions; 50 proteins exhibited at least 2-fold differences between these two clones. These 50 proteins were analyzed by GeneGo and were found to be associated with liver neoplasms, hepatocellular carcinoma (HCC), and liver diseases. They were also components of metabolic pathways, immune responses, and cytoskeleton remodeling. Among these proteins, the expressions of S100P, S100A14, and vimentin were verified in several HCC cell lines, and their expressions were correlated with tumorigenicity in HCC cell lines. The functional significance of vimentin and S100A14 were also investigated and verified.
authors.affiliation: Strategic Business and Innovation Technology Development Division, Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, 195 Sec.4 Chung Hsing Road, Chutung, 31040 Hsinchu, Taiwan.
authors.forename: Ching-Huai
authors.initials: CH
authors.lastname: Ko
authors.forename: Chieh-Fang
authors.initials: CF
authors.lastname: Cheng
authors.forename: Chin-Pen
authors.initials: CP
authors.lastname: Lai
authors.forename: Te-Hui
authors.initials: TH
authors.lastname: Tzu
authors.forename: Chih-Wei
authors.initials: CW
authors.lastname: Chiu
authors.forename: Mei-Wei
authors.initials: MW
authors.lastname: Lin
authors.forename: Si-Yuan
authors.initials: SY
authors.lastname: Wu
authors.forename: Chung-Yuan
authors.initials: CY
authors.lastname: Sun
authors.forename: Hsiang-Wen
authors.initials: HW
authors.lastname: Tseng
authors.forename: Chun-Chung
authors.initials: CC
authors.lastname: Wang
authors.forename: Zong-Keng
authors.initials: ZK
authors.lastname: Kuo
authors.forename: Ling-Mei
authors.initials: LM
authors.lastname: Wang
authors.forename: Sung-Fang
authors.initials: SF
authors.lastname: Chen
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D013058:Mass Spectrometry; D058977:Molecular Sequence Annotation; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D020543:Proteome / Q000235:genetics* / Q000378:metabolism; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism; D013194:Staining and Labeling / Q000379:methods; D014746:Vimentin / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D020543:Proteome; D009418:S100 Proteins; D014746:Vimentin