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.
Highlights
Hepatocellular carcinoma (HCC) is the fifth most common malignant neoplasm worldwide [1]
The integrin α6 protein cannot be detected by Western blotting from immuno-complex mixtures immunoprecipitated by CD151 monoclonal antibody (mAb) 9B, whereas integrin α6 can be detected from immuno-complex mixtures immunoprecipitated by the other anti-CD151 antibody
These results may indicate that CD151 mAb 9B competitively binds to the epitope through which integrin α6 binds to CD151 (Figure 1E)
Summary
Hepatocellular carcinoma (HCC) is the fifth most common malignant neoplasm worldwide [1]. Tetraspanin CD151, one of the most important members of the tetraspanins, has been identified as an important player in physiological processes [6] and the progression of malignant tumors [7], including skin [8], pancreas [9], lung [10], colon [11] and breast tumors [12, 13]. We validated the role of the CD151/integrin α6β1 complex in the progression of HCC [16]. Both CD151 and CD151-enriched microdomains appears to be promising targets in the treatment of HCC [17]. Simple inhibition of CD151 in HCC is inappropriate because CD151 plays essential roles in normal physiological processes, including cell adhesion, motility, activation and proliferation [6, 18,19,20]. Based on the above evidence, the dissociation of CD151-depedent TEM could be an effective strategy for inhibiting CD151’s tumorpromoting abilities without disrupting its physiological functions [17]
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