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 MenaINV isoform drives invasion, intravasation and metastasis. However, the abundance and distribution of endogenously expressed MenaINV 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 MenaINV isoform-specific monoclonal antibody and used it to examine MenaINV expression patterns in mouse mammary and human breast tumors. MenaINV expression increases during tumor progression and to examine the relationship between MenaINV expression and markers for epithelial or mesenchymal status, stemness, stromal cell types and hypoxic regions. Further, while MenaINV 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-MenaINV-isoform specific antibody, and provide the first description of endogenous MenaINV protein expression in mouse and human tumors.