TY - JOUR
T1 - 1B50-1, a mAb raised against recurrent tumor cells, targets liver tumor-initiating cells by binding to the calcium channel α2δ1 subunit
AU - Zhao, Wei
AU - Wang, Limin
AU - Han, Haibo
AU - Jin, Kemin
AU - Lin, Na
AU - Guo, Ting
AU - Chen, Yangde
AU - Cheng, Heping
AU - Lu, Fengmin
AU - Fang, Weigang
AU - Wang, Yu
AU - Xing, Baocai
AU - Zhang, Zhiqian
N1 - Funding Information:
Thanks are given to Professor Cheng Qian for providing the Huh7 cell line and to the FACS Core Facility of Peking University Cancer Hospital for performing FACS assays. This work was supported by the National Basic Research Program of China (the “973” Program, No. 2010CB529402), National Natural Science Foundation of China (grant numbers 81071733 and 31221002), the “863” Project (2007AA02Z133), Beijing NSF (5122012), and Beijing Outstanding Talents Training Funds in Health Sciences (grant No. 2011-2-24). Y.C. is an employee of Genzyme, a Sanofi Company.
PY - 2013/4/15
Y1 - 2013/4/15
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ccr.2013.02.025
DO - 10.1016/j.ccr.2013.02.025
M3 - Article
C2 - 23597567
AN - SCOPUS:84876395186
SN - 1535-6108
VL - 23
SP - 541
EP - 556
JO - Cancer cell
JF - Cancer cell
IS - 4
ER -