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http://purl.uniprot.org/citations/23758976http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/23758976http://www.w3.org/2000/01/rdf-schema#comment"

Background

Nectin-2 is a Ca(2+)-independent cell-cell adhesion molecule that is one of the plasma membrane components of adherens junctions. However, little has been reported about the involvement of Nectin-2 in cancer.

Methods

To determine the expression of Nectin-2 in cancer tissues and cancer cell lines, we performed gene expression profile analysis, immunohistochemistry studies, and flow cytometry analysis. We also investigated the potential of this molecule as a target for antibody therapeutics to treat cancers by generating and characterizing an anti-Nectin-2 rabbit polyclonal antibody (poAb) and 256 fully human anti-Nectin-2 monoclonal antibodies (mAbs). In addition, we tested anti-Nectin-2 mAbs in several in vivo tumor growth inhibition models to investigate the primary mechanisms of action of the mAbs.

Results

In the present study, we found that Nectin-2 was over-expressed in clinical breast and ovarian cancer tissues by using gene expression profile analysis and immunohistochemistry studies. Nectin-2 was over-expressed in various cancer cell lines as well. Furthermore, the polyclonal antibody specific to Nectin-2 suppressed the in vitro proliferation of OV-90 ovarian cancer cells, which express endogenous Nectin-2 on the cell surface. The anti-Nectin-2 mAbs we generated were classified into 7 epitope bins. The anti-Nectin-2 mAbs demonstrated antibody-dependent cellular cytotoxicity (ADCC) and epitope bin-dependent features such as the inhibition of Nectin-2-Nectin-2 interaction, Nectin-2-Nectin-3 interaction, and in vitro cancer cell proliferation. A representative anti-Nectin-2 mAb in epitope bin VII, Y-443, showed anti-tumor effects against OV-90 cells and MDA-MB-231 breast cancer cells in mouse therapeutic models, and its main mechanism of action appeared to be ADCC.

Conclusions

We observed the over-expression of Nectin-2 in breast and ovarian cancers and anti-tumor activity of anti-Nectin-2 mAbs via strong ADCC. These findings suggest that Nectin-2 is a potential target for antibody therapy against breast and ovarian cancers."xsd:string
http://purl.uniprot.org/citations/23758976http://purl.org/dc/terms/identifier"doi:10.1186/1476-4598-12-60"xsd:string
http://purl.uniprot.org/citations/23758976http://purl.uniprot.org/core/author"Ito Y."xsd:string
http://purl.uniprot.org/citations/23758976http://purl.uniprot.org/core/author"Oshima T."xsd:string
http://purl.uniprot.org/citations/23758976http://purl.uniprot.org/core/author"Sato S."xsd:string
http://purl.uniprot.org/citations/23758976http://purl.uniprot.org/core/author"Watanabe T."xsd:string
http://purl.uniprot.org/citations/23758976http://purl.uniprot.org/core/author"Kato J."xsd:string
http://purl.uniprot.org/citations/23758976http://purl.uniprot.org/core/author"Kurokawa T."xsd:string
http://purl.uniprot.org/citations/23758976http://purl.uniprot.org/core/author"Kokubo T."xsd:string
http://purl.uniprot.org/citations/23758976http://purl.uniprot.org/core/author"Hori A."xsd:string
http://purl.uniprot.org/citations/23758976http://purl.uniprot.org/core/author"Tsuji I."xsd:string
http://purl.uniprot.org/citations/23758976http://purl.uniprot.org/core/date"2013"xsd:gYear
http://purl.uniprot.org/citations/23758976http://purl.uniprot.org/core/name"Mol Cancer"xsd:string
http://purl.uniprot.org/citations/23758976http://purl.uniprot.org/core/pages"60"xsd:string
http://purl.uniprot.org/citations/23758976http://purl.uniprot.org/core/title"Nectin-2 is a potential target for antibody therapy of breast and ovarian cancers."xsd:string
http://purl.uniprot.org/citations/23758976http://purl.uniprot.org/core/volume"12"xsd:string
http://purl.uniprot.org/citations/23758976http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/23758976
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http://purl.uniprot.org/uniprot/Q92692#attribution-86495C9CAD1FFB2D1702882BD68C59CAhttp://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/23758976
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