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Abstract
Background: Triple Negative Breast Cancers (TNBC) are the most aggressive breast cancers and lead to poor prognoses. This is due to a high resistance to therapies, mainly because of the presence of Cancer Stem Cells (CSCs). Plasticity, a feature of CSCs, is acquired through the Epithelial to Mesenchymal Transition (EMT), a process that has been recently shown to be regulated by a key molecule, CD146. Of interest, CD146 is over-expressed in TNBC. Methods: The MDA-MB-231 TNBC cell line was used as a model to study the role of CD146 and its secreted soluble form (sCD146) in the development and dissemination of TNBC using in vitro and in vivo studies. Results: High expression of CD146 in a majority of MDA-MB-231 cells leads to an increased secretion of sCD146 that up-regulates the expression of EMT and CSC markers on the cells. These effects can be blocked with a specific anti-sCD146 antibody, M2J-1 mAb. M2J-1 mAb was able to reduce tumour development and dissemination in a model of cells xenografted in nude mice and an experimental model of metastasis, respectively, in part through its effects on CSC. Conclusion: We propose that M2J-1 mAb could be used as an additional therapeutic approach to fight TNBC.
Highlights
CD146, known as MUC18 or MCAM, is a 113KDa transmembrane glycoprotein that was first described by Johnson et al as a melanoma progression antigen [1]
CD146 induces the epithelial-to-mesenchymal transition (EMT), a crucial process in cancer metastasis [11], gaining stem cell-like properties [12] and generating cells known as Cancer Stem Cells (CSC)
We recently showed that CD146 expressed on cancer cells can generate a soluble form that is secreted and displays growth, metastatic and angiogenic properties in different cancer models [17]
Summary
CD146, known as MUC18 or MCAM, is a 113KDa transmembrane glycoprotein that was first described by Johnson et al as a melanoma progression antigen [1]. Triple Negative Breast Cancers (TNBC) are the most aggressive breast cancers and lead to poor prognoses This is due to a high resistance to therapies, mainly because of the presence of Cancer Stem Cells (CSCs). Results: High expression of CD146 in a majority of MDA-MB-231 cells leads to an increased secretion of sCD146 that up-regulates the expression of EMT and CSC markers on the cells. These effects can be blocked with a specific anti-sCD146 antibody, M2J-1 mAb. M2J-1 mAb was able to reduce tumour development and dissemination in a model of cells xenografted in nude mice and an experimental model of metastasis, respectively, in part through its effects on CSC. Conclusion: We propose that M2J-1 mAb could be used as an additional therapeutic approach to fight TNBC
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