[PDF][PDF] Macrophage binding to receptor VCAM-1 transmits survival signals in breast cancer cells that invade the lungs

Q Chen, XHF Zhang, J Massagué - Cancer cell, 2011 - cell.com
Cancer cell, 2011cell.com
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 …
Summary
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.
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