Characterization of the expression of the pro-metastatic Mena(INV) isoform during breast tumor progression

Clin Exp Metastasis. 2016 Mar;33(3):249-61. doi: 10.1007/s10585-015-9775-5. Epub 2015 Dec 17.


Several functionally distinct isoforms of the actin regulatory Mena are produced by alternative splicing during tumor progression. Forced expression of the Mena(INV) isoform drives invasion, intravasation and metastasis. However, the abundance and distribution of endogenously expressed Mena(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(INV) isoform-specific monoclonal antibody and used it to examine Mena(INV) expression patterns in mouse mammary and human breast tumors. Mena(INV) expression increases during tumor progression and to examine the relationship between Mena(INV) expression and markers for epithelial or mesenchymal status, stemness, stromal cell types and hypoxic regions. Further, while Mena(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(INV)-isoform specific antibody, and provide the first description of endogenous Mena(INV) protein expression in mouse and human tumors.

Keywords: Breast cancer; Hypoxia; Mena; Metastasis; Microenvironment; Stemness.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • Biomarkers, Tumor / analysis*
  • Blotting, Western
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Cytoskeletal Proteins / analysis
  • Cytoskeletal Proteins / biosynthesis
  • Disease Progression
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Heterografts
  • Humans
  • Image Processing, Computer-Assisted
  • Immunohistochemistry
  • Mammary Neoplasms, Experimental / pathology
  • Mice
  • Mice, Transgenic
  • Microfilament Proteins / analysis
  • Microfilament Proteins / biosynthesis*
  • Protein Isoforms / analysis
  • Protein Isoforms / biosynthesis


  • Antibodies, Monoclonal
  • Biomarkers, Tumor
  • Cytoskeletal Proteins
  • Enah protein, human
  • Enah protein, mouse
  • Microfilament Proteins
  • Protein Isoforms