Characterization of the expression of the pro-metastatic MenaINV isoform during breast tumor progression

Abstract

Several functionally distinct isoforms of the actin regulatory Mena are produced by alternative splicing during tumor progression. Forced expression of the Mena[superscript INV] isoform drives invasion, intravasation and metastasis. However, the abundance and distribution of endogenously expressed Mena[superscript INV] within primary tumors during progression remain unknown, as most studies to date have only assessed relative mRNA levels from dissociated tumor samples. We have developed a Mena[superscript INV] isoform-specific monoclonal antibody and used it to examine Mena[superscript INV]expression patterns in mouse mammary and human breast tumors. Mena[superscript INV] expression increases during tumor progression and to examine the relationship between Mena[superscript INV] expression and markers for epithelial or mesenchymal status, stemness, stromal cell types and hypoxic regions. Further, while Mena[superscript INV] robustly expressed in vascularized areas of the tumor, it is not confined to cells adjacent to blood vessels. Altogether, these data demonstrate the specificity and utility of the anti-Mena[superscript INV]-isoform specific antibody, and provide the first description of endogenous Mena[superscript INV]protein expression in mouse and human tumors.