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

Evanthia T. Roussos, Sumanta Goswami, Michele Balsamo, Yarong Wang, Robert Stobezki, Esther Adler, Brian D. Robinson, Joan G. Jones, Frank B. Gertler, John S. Condeelis, Maja H. Oktay

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

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 (MenaINV) 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-MenaINV 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 MenaINV is the isoform associated with breast cancer cell discohesion, invasion and intravasation in mice and in humans. They also imply that MenaINV expression and TMEM score measure related aspects of a common tumor cell dissemination mechanism and provide new insight into metastatic risk.

Original languageEnglish (US)
Pages (from-to)515-527
Number of pages13
JournalClinical and Experimental Metastasis
Volume28
Issue number6
DOIs
StatePublished - Aug 2011

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Protein Isoforms
Breast Neoplasms
Neoplasms
Macrophages
Carcinoma, Ductal, Breast
Ductal Carcinoma
Tumor Microenvironment
Fine Needle Biopsy
Heterografts
Cell Movement
Actins
Neoplasm Metastasis
Messenger RNA
Proteins

Keywords

  • Breast cancer
  • Cell motility
  • Intravasation
  • Metastasis
  • TMEM

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Mena invasive (MenaINV) and Mena11a isoforms play distinct roles in breast cancer cell cohesion and association with TMEM. / Roussos, Evanthia T.; Goswami, Sumanta; Balsamo, Michele; Wang, Yarong; Stobezki, Robert; Adler, Esther; Robinson, Brian D.; Jones, Joan G.; Gertler, Frank B.; Condeelis, John S.; Oktay, Maja H.

In: Clinical and Experimental Metastasis, Vol. 28, No. 6, 08.2011, p. 515-527.

Research output: Contribution to journalArticle

Roussos, Evanthia T. ; Goswami, Sumanta ; Balsamo, Michele ; Wang, Yarong ; Stobezki, Robert ; Adler, Esther ; Robinson, Brian D. ; Jones, Joan G. ; Gertler, Frank B. ; Condeelis, John S. ; Oktay, Maja H. / Mena invasive (MenaINV) and Mena11a isoforms play distinct roles in breast cancer cell cohesion and association with TMEM. In: Clinical and Experimental Metastasis. 2011 ; Vol. 28, No. 6. pp. 515-527.
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abstract = "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 (MenaINV) 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-MenaINV 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 MenaINV is the isoform associated with breast cancer cell discohesion, invasion and intravasation in mice and in humans. They also imply that MenaINV expression and TMEM score measure related aspects of a common tumor cell dissemination mechanism and provide new insight into metastatic risk.",
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AU - Roussos, Evanthia T.

AU - Goswami, Sumanta

AU - Balsamo, Michele

AU - Wang, Yarong

AU - Stobezki, Robert

AU - Adler, Esther

AU - Robinson, Brian D.

AU - Jones, Joan G.

AU - Gertler, Frank B.

AU - Condeelis, John S.

AU - Oktay, Maja H.

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AB - 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 (MenaINV) 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-MenaINV 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 MenaINV is the isoform associated with breast cancer cell discohesion, invasion and intravasation in mice and in humans. They also imply that MenaINV expression and TMEM score measure related aspects of a common tumor cell dissemination mechanism and provide new insight into metastatic risk.

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