Mena invasive (Mena(INV)) and Mena11a isoforms play distinct roles in breast cancer cell cohesion and association with TMEM.

TitleMena invasive (Mena(INV)) and Mena11a isoforms play distinct roles in breast cancer cell cohesion and association with TMEM.
Publication TypeJournal Article
Year of Publication2011
AuthorsRoussos, ET, Goswami, S, Balsamo, M, Wang, Y, Stobezki, R, Adler, E, Robinson, BD, Jones, JG, Gertler, FB, Condeelis, JS, Oktay, MH
JournalClin Exp Metastasis
Date Published2011 Aug
KeywordsAnimals, Breast Neoplasms, Cell Adhesion, Cytoskeletal Proteins, Female, Gene Expression Regulation, Neoplastic, Humans, Mammary Neoplasms, Experimental, Mice, Mice, SCID, Neoplasm Metastasis, Protein Isoforms, Tumor Cells, Cultured, Tumor Microenvironment

Mena, an actin regulatory protein, functions at the convergence of motility pathways that drive breast cancer cell invasion and migration in vivo. The tumor microenvironment spontaneously induces both increased expression of the Mena invasive (Mena(INV)) and decreased expression of Mena11a isoforms in invasive and migratory tumor cells. Tumor cells with this Mena expression pattern participate with macrophages in migration and intravasation in mouse mammary tumors in vivo. Consistent with these findings, anatomical sites containing tumor cells with high levels of Mena expression associated with perivascular macrophages were identified in human invasive ductal breast carcinomas and called TMEM. The number of TMEM sites positively correlated with the development of distant metastasis in humans. Here we demonstrate that mouse mammary tumors generated from EGFP-Mena(INV) expressing tumor cells are significantly less cohesive and have discontinuous cell-cell contacts compared to Mena11a xenografts. Using the mouse PyMT model we show that metastatic mammary tumors express 8.7 fold more total Mena and 7.5 fold more Mena(INV) mRNA than early non-metastatic ones. Furthermore, Mena(INV) expression in fine needle aspiration biopsy (FNA) samples of human invasive ductal carcinomas correlate with TMEM score while Mena11a does not. These results suggest that Mena(INV) is the isoform associated with breast cancer cell discohesion, invasion and intravasation in mice and in humans. They also imply that Mena(INV) expression and TMEM score measure related aspects of a common tumor cell dissemination mechanism and provide new insight into metastatic risk.

Alternate JournalClin. Exp. Metastasis
PubMed ID21484349
PubMed Central IDPMC3459587
Grant ListCA100324 / CA / NCI NIH HHS / United States
CA113395 / CA / NCI NIH HHS / United States
CA150344 / CA / NCI NIH HHS / United States
GM58801 / GM / NIGMS NIH HHS / United States
R01 GM058801-12 / GM / NIGMS NIH HHS / United States
U54CA112967 / CA / NCI NIH HHS / United States