Macrophage Binding to Receptor VCAM-1 Transmits Survival Signals in Breast Cancer Cells that Invade the Lungs
Cette étude identifie le rôle joué par la molécule d'adhérence cellulaire vasculaire VCAM-1 dans la formation de métastases pulmonaires d'un cancer du sein
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 ±4-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 ±4-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. º Breast cancer cells expressing VCAM-1 have a survival advantage in the lungs º Macrophage binding to VCAM-1 on cancer cells triggers Akt survival signal via Ezrin º VCAM-1 primes cancer cells for residence in leukocyte-rich microenvironments º Blocking the VCAM-1-±4-integrin interaction enhances cancer cell death
Cancer Cell 2011