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However, targeting CD146 remains challenging since it is also expressed on other cell types, as vessel cells, where it displays important physiological functions. We previously demonstrated that CD146 is shed as a soluble form (sCD146) that vectorizes the effects of membrane CD146 on tumor angiogenesis, growth and survival. We thus generated a novel monoclonal antibody, the M2J\u20101 mAb, which specifically targets sCD146, but not membrane CD146, and counteracts these effects. In our study, we analyzed the effects of sCD146 on the dissemination and the associated procoagulant phenotype in two highly invasive human CD146\u2010positive cancer cell lines (ovarian and melanoma). Results show that sCD146 induced epithelial to mesenchymal transition, favored the generation of cancer stem cells and increased the membrane expression of tissue factor. Treatment of cancer cells with sCD146 in two experimental models (subcutaneous xenografting and intracardiac injection of cancer cells in nude mice) led to increased tumor dissemination and procoagulant activity. The M2J\u20101 mAb drastically reduced metastasis but also procoagulant activity, in particular by decreasing the number of circulating tumor microparticles, and blocked the relevant signaling pathways as demonstrated by RNA expression profiling experiments. Thus, our findings demonstrate that sCD146 mediates important pro\u2010metastatic and procoagulant effects in two CD146\u2010positive tumors. Targeting sCD146 with the newly generated M2J\u20101 mAb could constitute an innovative strategy for preventing dissemination and thromboembolism in many CD146\u2010positive tumors.<\/jats:p>","DOI":"10.1002\/ijc.32909","type":"journal-article","created":{"date-parts":[[2020,2,5]],"date-time":"2020-02-05T12:35:45Z","timestamp":1580906145000},"page":"1666-1679","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Therapeutic targeting of soluble CD146\/MCAM with the M2J\u20101 monoclonal antibody prevents metastasis development and procoagulant activity in CD146\u2010positive invasive tumors"],"prefix":"10.1002","volume":"147","author":[{"given":"Jimmy","family":"Stalin","sequence":"first","affiliation":[{"name":"INSERM, INRAE, C2VN, UFR Pharmacie Aix\u2010Marseille University  Marseille 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