title: Efficacy of using cancer stem cell markers in isolating and characterizing liver cancer stem cells.
abstract: Recent evidence suggests that a subset of hepatocellular carcinomas (HCCs) are derived from liver cancer stem cells (LCSCs). In order to isolate and characterize LCSCs, reliable markers that are specific to these cells are required. We evaluated the efficacy of a range of cancer stem cell (CSC) markers in isolating and characterizing LCSCs. We show that the most widely used CSC markers are not specific to LCSCs. By western analysis, protein expression of the common markers showed no significant difference between HCC tumor tissues and adjacent non-cancerous liver. Further, isolation of LCSCs from common HCC cell lines using FACScan and microbeads showed no consistent marker expression pattern. We also show that LCSCs have unique subtypes. Immunohistochemistry of HCC tissues showed that different HCCs express unique combinations of LCSC markers. Quantitative real-time polymerase chain reaction analysis showed that LCSCs isolated using different markers in the same HCC phenotype had different expression profiles. Likewise, LCSCs isolated from different HCC phenotypes with the same marker also had unique expression profiles and displayed varying resistance profiles to Sorafenib. Thus, using a range of commonly used CSC markers in HCCs and cell lines, we demonstrate that currently available markers are not specific for LCSCs. LCSCs have unique subtypes that express distinctive combinations of LCSC markers and altered drug resistance profiles, making their identification problematic.
authors: 1 Storr Liver Unit, Westmead Millennium Institute, The University of Sydney and Westmead Hospital , Westmead, Australia .
authors: George S
authors: GS
authors: Wilson
authors: Zenan
authors: Z
authors: Hu
authors: Wei
authors: W
authors: Duan
authors: Aiping
authors: A
authors: Tian
authors: Xin M
authors: XM
authors: Wang
authors: Duncan
authors: D
authors: McLeod
authors: Vincent
authors: V
authors: Lam
authors: Jacob
authors: J
authors: George
authors: Liang
authors: L
authors: Qiao
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019008:Drug Resistance, Neoplasm; D000071858:Epithelial Cell Adhesion Molecule; D020869:Gene Expression Profiling; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000378:metabolism*; D009536:Niacinamide / Q000031:analogs & derivatives / Q000494:pharmacology; D010455:Peptides / Q000378:metabolism; D010671:Phenylurea Compounds / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D000077157:Sorafenib; D018800:Thy-1 Antigens / Q000378:metabolism; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D000071916:AC133 Antigen; C097353:AFP protein, human; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D006023:Glycoproteins; D018960:Hyaluronan Receptors; D010455:Peptides; D010671:Phenylurea Compounds; D018800:Thy-1 Antigens; D000509:alpha-Fetoproteins; D009536:Niacinamide; D000077157:Sorafenib
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