Macrophage binding to receptor VCAM-1 transmits survival signals in breast cancer cells that invade the lungs Journal Article

   

Authors:	Chen, Q.; Zhang, X. F.; Massague, J.
Article Title:	Macrophage binding to receptor VCAM-1 transmits survival signals in breast cancer cells that invade the lungs
Abstract:	Aberrant expression of vascular cell adhesion molecule-1 (VCAM-1) in breast cancer cells is associated with lung relapse, but the role of VCAM-1 as a mediator of metastasis has remained unknown. We report that VCAM-1 provides a survival advantage to breast cancer cells that infiltrate leukocyte-rich microenvironments such as the lungs. VCAM-1 tethers metastasis-associated macrophages to cancer cells via counter-receptor α4-integrins. Clustering of cell surface VCAM-1, acting through Ezrin, triggers Akt activation and protects cancer cells from proapoptotic cytokines such as TRAIL. This prosurvival function of VCAM-1 can be blocked by antibodies against α4-integrins. Thus, newly disseminated cancer cells expressing VCAM-1 can thrive in leukocyte-rich microenvironments through juxtacrine activation of a VCAM-1-Ezrin-PI3K/Akt survival pathway. © 2011 Elsevier Inc.
Keywords:	signal transduction; protein kinase b; human tissue; protein expression; protein phosphorylation; nonhuman; protein function; animal cell; mouse; animals; mice; animal tissue; cell survival; apoptosis; breast cancer; cell infiltration; protein protein interaction; lung neoplasms; vascular cell adhesion molecule 1; animal experiment; animal model; enzyme activation; breast neoplasms; lung metastasis; neoplastic cells, circulating; cancer cell; tumor necrosis factor related apoptosis inducing ligand; macrophage; macrophages; cell adhesion; cell invasion; leukocyte; breast cell; ezrin; cytoskeletal proteins; cell surface; tumor microenvironment; vascular cell adhesion molecule-1; leukocytes; oncogene protein v-akt; alpha4 integrin
Journal Title:	Cancer Cell
Volume:	20
Issue:	4
ISSN:	1535-6108
Publisher:	Cell Press
Date Published:	2011-10-18
Start Page:	538
End Page:	549
Language:	English
DOI:	10.1016/j.ccr.2011.08.025
PROVIDER:	scopus
PUBMED:	22014578
PMCID:	PMC3293160
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-80054725681&partnerID=40&md5=2324ff1383bcea12f5d1f87d60015f6a
Notes:	--- - "Export Date: 9 December 2011" - "CODEN: CCAEC" - "Source: Scopus"

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