title: 1B50-1, a mAb raised against recurrent tumor cells, targets liver tumor-initiating cells by binding to the calcium channel α2δ1 subunit.
abstract: 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.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cell Biology, Peking University Cancer Hospital and Institute, Beijing 100142, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.forename: Limin
authors.initials: L
authors.lastname: Wang
authors.forename: Haibo
authors.initials: H
authors.lastname: Han
authors.forename: Kemin
authors.initials: K
authors.lastname: Jin
authors.forename: Na
authors.initials: N
authors.lastname: Lin
authors.forename: Ting
authors.initials: T
authors.lastname: Guo
authors.forename: Yangde
authors.initials: Y
authors.lastname: Chen
authors.forename: Heping
authors.initials: H
authors.lastname: Cheng
authors.forename: Fengmin
authors.initials: F
authors.lastname: Lu
authors.forename: Weigang
authors.initials: W
authors.lastname: Fang
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Baocai
authors.initials: B
authors.lastname: Xing
authors.forename: Zhiqian
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D015220:Calcium Channels / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009364:Neoplasm Recurrence, Local / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D015220:Calcium Channels