Article ID Journal Published Year Pages File Type
2108098 Cancer Cell 2013 16 Pages PDF
Abstract

SummaryThe identification and targeted therapy of cells involved in hepatocellular carcinoma (HCC) recurrence remain challenging. Here, we generated a monoclonal antibody against recurrent HCC, 1B50-1, that bound the isoform 5 of the α2δ1 subunit of voltage-gated calcium channels and identified a subset of tumor-initiating cells (TICs) with stem cell-like properties. A surgical margin with cells detected by 1B50-1 predicted rapid recurrence. Furthermore, 1B50-1 had a therapeutic effect on HCC engraftments by eliminating TICs. Finally, α2δ1 knockdown reduced self-renewal and tumor formation capacities and induced apoptosis of TICs, whereas its overexpression led to enhanced sphere formation, which is regulated by calcium influx. Thus, α2δ1 is a functional liver TIC marker, and its inhibitors may serve as potential anti-HCC drugs.

► 1B50-1, which recognizes α2δ1, identifies HCC tumor-initiating cells ► A surgical margin with cells detected by 1B50-1 correlates with poor HCC prognosis ► α2δ1 is essential in Ca2+ signaling and maintenance of TIC properties ► 1B50-1 has a therapeutic effect on HCC by eradicating α2δ1+ TICs

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Life Sciences Biochemistry, Genetics and Molecular Biology Cancer Research
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