CD24(+) liver tumor-initiating cells drive self-renewal and tumor initiation through STAT3-mediated NANOG regulation.
Cell Stem Cell, 2011/7/08;9(1):50-63.
Lee TK[1], Castilho A, Cheung VC, Tang KH, Ma S, Ng IO
Affiliations
PMID: 21726833DOI: 10.1016/j.stem.2011.06.005
Impact factor: 25.269
Abstract
Tumor-initiating cells (T-ICs) are a subpopulation of chemoresistant tumor cells that have been shown to cause tumor recurrence upon chemotherapy. Identification of T-ICs and their related pathways are therefore priorities for the development of new therapeutic paradigms. We established chemoresistant hepatocellular carcinoma (HCC) xenograft tumors in immunocompromised mice in which an enriched T-IC population was capable of tumor initiation and self-renewal. With this model, we found CD24 to be upregulated in residual chemoresistant tumors when compared with bulk tumor upon cisplatin treatment. CD24(+) HCC cells were found to be critical for the maintenance, self-renewal, differentiation, and metastasis of tumors and to significantly impact patients' clinical outcome. With a lentiviral-based knockdown approach, CD24 was found to be a functional liver T-IC marker that drives T-IC genesis through STAT3-mediated NANOG regulation. Our findings point to a CD24 cascade in liver T-ICs that may provide an attractive therapeutic target for HCC patients.
MeSH terms
Adult; Aged; Aged, 80 and over; Animals; CD24 Antigen; Carcinoma, Hepatocellular; Cell Differentiation; Cell Line, Tumor; Cell Proliferation; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Homeodomain Proteins; Humans; Liver Neoplasms; Mice; Middle Aged; Nanog Homeobox Protein; Neoplasm Metastasis; Neoplastic Stem Cells; Phosphorylation; STAT3 Transcription Factor; Up-Regulation; Xenograft Model Antitumor Assays
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