Clinical & Experimental Metastasis

, Volume 28, Issue 6, pp 515–527 | Cite as

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 Paper

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 MenaINV mRNA than early non-metastatic ones. Furthermore, MenaINV 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.

Keywords

Breast cancer Metastasis Cell motility Intravasation TMEM 

Abbreviations

EGF

Epidermal growth factor

EGFP

Enhanced green fluorescent protein

FACs

Fluorescence activated cell sorting

FFPE

Formalin-fixed paraffin-embedded

FNA

Fine needle aspiration

IHC

Immunohistochemistry

IF

Immunofluorescence

IVI

Intravital imaging

qRT-PCR

Quantitative real time polymerase chain reaction

SCID

Severe combined immunodeficiency

TMEM

Tumor microenvironment for metastasis

APTC

Average primary tumor cells

Supplementary material

10585_2011_9388_MOESM1_ESM.docx (817 kb)
Supplementary material 1 (DOCX 816 kb)

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Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Evanthia T. Roussos
    • 1
  • Sumanta Goswami
    • 1
    • 4
  • Michele Balsamo
    • 3
  • Yarong Wang
    • 1
  • Robert Stobezki
    • 4
  • Esther Adler
    • 7
  • Brian D. Robinson
    • 5
  • Joan G. Jones
    • 6
  • Frank B. Gertler
    • 3
  • John S. Condeelis
    • 1
    • 2
  • Maja H. Oktay
    • 7
  1. 1.Department of Anatomy and Structural BiologyAlbert Einstein College of MedicineBronxUSA
  2. 2.Gruss Lipper Biophotonics CenterAlbert Einstein College of MedicineBronxUSA
  3. 3.David H Koch Institute for Integrative Cancer ResearchMassachusetts Institute of TechnologyCambridgeUSA
  4. 4.Department of BiologyYeshiva UniversityNew YorkUSA
  5. 5.Department of PathologyJohns Hopkins HospitalBaltimoreUSA
  6. 6.Department of Pathology and Laboratory MedicineWeill Cornell Medical CollegeNew YorkUSA
  7. 7.Department of PathologyMontefiore Medical CenterBronxUSA

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