title: Characterization of the expression of the pro-metastatic Mena(INV) 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(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.
authors.affiliation: Koch Institute for Integrative Cancer Research, MIT, 76-317, 77 Massachusetts Ave, Cambridge, MA, 02139, USA. mjoudin@mit.edu.
authors.forename: Madeleine J
authors.initials: MJ
authors.lastname: Oudin
authors.affiliation: Koch Institute for Integrative Cancer Research, MIT, 76-317, 77 Massachusetts Ave, Cambridge, MA, 02139, USA.|Department of Biological Engineering, MIT, Cambridge, MA, 02139, USA.
authors.forename: Shannon K
authors.initials: SK
authors.lastname: Hughes
authors.affiliation: Koch Institute for Integrative Cancer Research, MIT, 76-317, 77 Massachusetts Ave, Cambridge, MA, 02139, USA.
authors.forename: Nazanin
authors.initials: N
authors.lastname: Rohani
authors.affiliation: Department of Biological Engineering, MIT, Cambridge, MA, 02139, USA.
authors.forename: Mira N
authors.initials: MN
authors.lastname: Moufarrej
authors.affiliation: Integrated Imaging Program, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
authors.forename: Joan G
authors.initials: JG
authors.lastname: Jones
authors.affiliation: Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
authors.forename: John S
authors.initials: JS
authors.lastname: Condeelis
authors.affiliation: Koch Institute for Integrative Cancer Research, MIT, 76-317, 77 Massachusetts Ave, Cambridge, MA, 02139, USA.|Department of Biological Engineering, MIT, Cambridge, MA, 02139, USA.
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Lauffenburger
authors.affiliation: Koch Institute for Integrative Cancer Research, MIT, 76-317, 77 Massachusetts Ave, Cambridge, MA, 02139, USA.|Department of Biology, MIT, Cambridge, MA, 02139, USA.
authors.forename: Frank B
authors.initials: FB
authors.lastname: Gertler
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000096:biosynthesis; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D064593:Heterografts; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008325:Mammary Neoplasms, Experimental / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000032:analysis / Q000096:biosynthesis*; D020033:Protein Isoforms / Q000032:analysis / Q000096:biosynthesis
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D003598:Cytoskeletal Proteins; C511939:Enah protein, human; C102176:Enah protein, mouse; D008840:Microfilament Proteins; D020033:Protein Isoforms
keywords: Breast cancer; Hypoxia; Mena; Metastasis; Microenvironment; Stemness