Mena invasive (MenaINV) and Mena11a isoforms play distinct roles in breast cancer cell cohesion and association with TMEM
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- 作者：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) - 关键词：Breast cancer ; Metastasis ; Cell motility ; Intravasation ; TMEM
- 刊名：Clinical & Experimental Metastasis
- 出版年：2011
- 出版时间：August 2011
- 年：2011
- 卷：28
- 期：6
- 页码：515-527
- 全文大小：718KB
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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. Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA
4. Department of Biology, Yeshiva University, New York, NY, 10033, USA
3. David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA
7. Department of Pathology, Montefiore Medical Center, Bronx, NY, 10467, USA
5. Department of Pathology, Johns Hopkins Hospital, Baltimore, MD, 21287, USA
6. Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, 10065, USA
2. Gruss Lipper Biophotonics Center, Albert Einstein College of Medicine, Bronx, NY, 10461, USA - ISSN：1573-7276
文摘
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.