Generation and characterization of a tetraspanin CD151/integrin '6β1-binding domain competitively binding monoclonal antibody for inhibition of tumor progression in HCC

被引:19
作者
Ke, Ai-Wu [1 ]
Zhang, Peng-Fei [1 ]
Shen, Ying-Hao [1 ]
Gao, Ping-Ting [1 ]
Dong, Zhao-Ru [1 ]
Zhang, Chi [1 ]
Cai, Jia-Bin [1 ]
Huang, Xiao-Yong [1 ]
Wu, Chao [2 ]
Zhang, Lu [1 ]
Kang, Qiang [3 ]
Liu, Li-Xin [3 ]
Xie, Nan [3 ]
Shen, Zao-Zhuo [1 ]
Hu, Mei-Yu [1 ]
Cao, Ya [4 ]
Qiu, Shuang-Jian [1 ]
Sun, Hui-Chuan [1 ]
Zhou, Jian [1 ]
Fan, Jia [1 ]
Shi, Guo-Ming [1 ]
机构
[1] Fudan Univ, Key Lab Carcinogenesis & Canc Invas, Zhongshan Hosp, Liver Canc Inst,Minist Educ, Shanghai 200032, Peoples R China
[2] Yangzhou Univ, Subei Peoples Hosp, Dept Hepatobiliary Surg, Yangzhou 225000, Jiangsu, Peoples R China
[3] Kunming Med Univ, Affiliated Hosp 2, Dept Hepatobiliary Surg, Kunming 650101, Peoples R China
[4] Cent South Univ, Xiangya Sch Med, Canc Res Inst, Changsha 410008, Hunan, Peoples R China
基金
中国国家自然科学基金;
关键词
hepatocellular carcinoma; tetraspanin CD151; integrin a 6 beta 1; monoclonal antibody; therapeutical agent; HEPATOCELLULAR-CARCINOMA; GENE-EXPRESSION; CD151; METASTASIS; IDENTIFICATION; HEPATITIS; CANCER;
D O I
10.18632/oncotarget.6833
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Our previous studies revealed that tetraspanin CD151 plays multiple roles in the progression of hepatocellular carcinoma (HCC) by forming a functional complex with integrin '6 beta 1. Herein, we generated a monoclonal antibody (mAb) that dissociates the CD151/integrin '6 beta 1 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 '6 beta 1 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 '6 beta 1-binding domain, which not only can displayed good reactivity to the CD151 antigen but also prevented tumor progression in HCC.
引用
收藏
页码:6314 / 6322
页数:9
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