Generation and characterization of a tetraspanin CD151/integrin α6β1-binding domain competitively binding monoclonal antibody for inhibition of tumor progression in HCC
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Ai-Wu Ke1,*, Peng-Fei Zhang1,*, Ying-Hao Shen1,*, Ping-Ting Gao1,*, Zhao-Ru Dong1,*, Chi Zhang1,*, Jia-Bin Cai1, Xiao-Yong Huang1, Chao Wu2, Lu Zhang1, Qiang Kang3, Li-Xin Liu3, Nan Xie3, Zao-Zhuo Shen1, Mei-Yu Hu1, Ya Cao4, Shuang-Jian Qiu1, Hui-Chuan Sun1, Jian Zhou1, Jia Fan1, Guo-Ming Shi1
1Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai 200032, P.R. China
2Department of Hepatobiliary Surgery, Subei People’s Hospital, Yangzhou University, Yangzhou 225000, China
3Department of Hepatobiliary Surgery, Second Affiliated Hospital of Kunming Medical University, Kunming 650101, China
4Cancer Research Institute, Xiangya School of Medicine, Central South University, Hunan 410008, China
*These authors have contributed equally to this work
Guo-Ming Shi, e-mail: email@example.com
Keywords: hepatocellular carcinoma, tetraspanin CD151, integrin α6β1, monoclonal antibody, therapeutical agent
Abbreviations: HCC, hepatocellular carcinoma; TEM, tetraspanin-enriched microdomains; TNM, tumor node metastasis; mAb, monoclonal antibody; EMT, epithelial-mesenchymal transition
Received: May 27, 2015 Accepted: December 29, 2015 Published: January 07, 2016
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.
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