Cancer cell, 2011-10, Vol.20 (4), p.538-549
2011
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Details
- Autor(en) / Beteiligte
- Titel
- Macrophage Binding to Receptor VCAM-1 Transmits Survival Signals in Breast Cancer Cells that Invade the Lungs
- Ist Teil von
- Cancer cell, 2011-10, Vol.20 (4), p.538-549
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2011
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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. [Display omitted] ► Breast cancer cells expressing VCAM-1 have a survival advantage in the lungs ► Macrophage binding to VCAM-1 on cancer cells triggers Akt survival signal via Ezrin ► VCAM-1 primes cancer cells for residence in leukocyte-rich microenvironments ► Blocking the VCAM-1-α4-integrin interaction enhances cancer cell death
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1535-6108eISSN: 1878-3686DOI: 10.1016/j.ccr.2011.08.025Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3293160
- Format
- –
- Schlagworte
- 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