title: Generation and characterization of a tetraspanin CD151/integrin α6β1-binding domain competitively binding monoclonal antibody for inhibition of tumor progression in HCC.
abstract: Our previous studies revealed that tetraspanin CD151 plays multiple roles in the progression of hepatocellular carcinoma (HCC) by forming a functional complex with integrin α6β1. Herein, we generated a monoclonal antibody (mAb) that dissociates the CD151/integrin α6β1 complex, and we evaluated its bioactivity in HCCs. A murine mAb, tetraspanin CD151 (IgG1, called CD151 mAb 9B), was successfully generated against the CD151-integrin α6β1 binding site of CD151 extracellular domains. Co-immunoprecipitation using CD151 mAb 9B followed by Western blotting detected a 28 kDa protein. Both immunofluorescent and immunohistochemical staining showed a good reactivity of CD151 mAb 9B in the plasma membrane and cytoplasm of HCC cells, as well as in liver cells. In vitro assays demonstrated that CD151 mAb 9B could inhibit neoangiogenesis and both the mobility and the invasiveness of HCC cells. An in vivo assay showed that CD151 mAb 9B inhibited tumor growth potential and HCC cells metastasis. We successfully produced a CD151 mAb 9B targeting the CD151/integrin α6β1-binding domain, which not only can displayed good reactivity to the CD151 antigen but also prevented tumor progression in HCC.
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai 200032, P.R. China.
authors.forename: Ai-Wu
authors.initials: AW
authors.lastname: Ke
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai 200032, P.R. China.
authors.forename: Peng-Fei
authors.initials: PF
authors.lastname: Zhang
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai 200032, P.R. China.
authors.forename: Ying-Hao
authors.initials: YH
authors.lastname: Shen
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai 200032, P.R. China.
authors.forename: Ping-Ting
authors.initials: PT
authors.lastname: Gao
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai 200032, P.R. China.
authors.forename: Zhao-Ru
authors.initials: ZR
authors.lastname: Dong
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai 200032, P.R. China.
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai 200032, P.R. China.
authors.forename: Jia-Bin
authors.initials: JB
authors.lastname: Cai
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai 200032, P.R. China.
authors.forename: Xiao-Yong
authors.initials: XY
authors.lastname: Huang
authors.affiliation: Department of Hepatobiliary Surgery, Subei People's Hospital, Yangzhou University, Yangzhou 225000, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wu
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai 200032, P.R. China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary Surgery, Second Affiliated Hospital of Kunming Medical University, Kunming 650101, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Kang
authors.affiliation: Department of Hepatobiliary Surgery, Second Affiliated Hospital of Kunming Medical University, Kunming 650101, China.
authors.forename: Li-Xin
authors.initials: LX
authors.lastname: Liu
authors.affiliation: Department of Hepatobiliary Surgery, Second Affiliated Hospital of Kunming Medical University, Kunming 650101, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Xie
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai 200032, P.R. China.
authors.forename: Zao-Zhuo
authors.initials: ZZ
authors.lastname: Shen
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai 200032, P.R. China.
authors.forename: Mei-Yu
authors.initials: MY
authors.lastname: Hu
authors.affiliation: Cancer Research Institute, Xiangya School of Medicine, Central South University, Hunan 410008, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai 200032, P.R. China.
authors.forename: Shuang-Jian
authors.initials: SJ
authors.lastname: Qiu
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai 200032, P.R. China.
authors.forename: Hui-Chuan
authors.initials: HC
authors.lastname: Sun
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai 200032, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai 200032, P.R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: Fan
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai 200032, P.R. China.
authors.forename: Guo-Ming
authors.initials: GM
authors.lastname: Shi
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000276:immunology* / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018450:Disease Progression; D056945:Hep G2 Cells; D006801:Humans; D039121:Integrin alpha6beta1 / Q000276:immunology*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D000072417:Protein Domains; D011897:Random Allocation; D060185:Tetraspanin 24 / Q000276:immunology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D039121:Integrin alpha6beta1; D060185:Tetraspanin 24
keywords: hepatocellular carcinoma; integrin α6β1; monoclonal antibody; tetraspanin CD151; therapeutical agent