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

Cancer Cell. 2011 Oct 18;20(4):538-49. doi: 10.1016/j.ccr.2011.08.025.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Adhesion / immunology
  • Cytoskeletal Proteins / metabolism
  • Female
  • Humans
  • Leukocytes / immunology
  • Leukocytes / metabolism
  • Leukocytes / pathology
  • Lung Neoplasms / secondary*
  • Macrophages / metabolism
  • Macrophages / physiology*
  • Mice
  • Neoplastic Cells, Circulating / immunology*
  • Neoplastic Cells, Circulating / metabolism
  • Oncogene Protein v-akt / metabolism
  • Signal Transduction
  • Vascular Cell Adhesion Molecule-1 / genetics*
  • Vascular Cell Adhesion Molecule-1 / immunology
  • Vascular Cell Adhesion Molecule-1 / metabolism


  • Cytoskeletal Proteins
  • Vascular Cell Adhesion Molecule-1
  • ezrin
  • Oncogene Protein v-akt