Generation and characterization of a tetraspanin CD151/integrin α6β1-binding domain competitively binding monoclonal antibody for inhibition of tumor progression in HCC.
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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四跨膜蛋白 CD151/整合素 α6β1 结合域竞争性结合单克隆抗体的生成和表征,用于抑制 HCC 中的肿瘤进展。
DOI:
10.18632/oncotarget.6833
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发表时间:
2016-02-02
期刊:
影响因子:
--
通讯作者:
Shi GM
中科院分区:
文献类型:
--
作者:
Ke AW;Zhang PF;Shen YH;Gao PT;Dong ZR;Zhang C;Cai JB;Huang XY;Wu C;Zhang L;Kang Q;Liu LX;Xie N;Shen ZZ;Hu MY;Cao Y;Qiu SJ;Sun HC;Zhou J;Fan J;Shi GM
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.