1B50-1, a mAb Raised against Recurrent Tumor Cells, Targets Liver Tumor-Initiating Cells by Binding to the Calcium Channel
Menée in vitro et à l'aide de xénogreffes, cette étude met en évidence des mécanismes par lesquels, en se liant à une sous-unité d'un canal calcique, un anticorps monoclonal appelé 1B50-1 induit une apoptose de cellules initiatrices de tumeurs d'un carcinome hépatocellulaire
The 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
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A surgical margin with cells detected by 1B50-1 correlates with poor HCC prognosis
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α2δ1 is essential in Ca2+ signaling and maintenance of TIC properties
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1B50-1 has a therapeutic effect on HCC by eradicating α2δ1+ TICs
Cancer cell , article en libre accès, 2012