Macrophage binding to receptor VCAM-1 transmits survival signals in breast cancer cells that invade the lungs
Open accessAbstract
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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The role of immune cells in cancer progression, such as macrophages, may differ between organs.
“We propose that cancer-immune cell interactions should be studied in organ-specific microfluidic models, since recent studies suggest that the role of immune cells in cancer progression, such as macrophages, may differ between organs[87].”
From Microfluidics: A New Tool for Modeling Cancer–Immune Interactions (2016) · cites this paper as [87]
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- Authors
- Chen, Q., Zhang, X. H.-F., & Massagué, J.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Massagué, Joan
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2011-10
- Volume
- 20
- Issue
- 4
- Pages
- 538-549
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC3293160
- OpenAlex
- W2007196889
- Cited by
- 619
- References
- 63
- Citations by year
- 2026: 25 · 2025: 38 · 2024: 44 · 2023: 52 · 2022: 50 · 2021: 59 · 2020: 48 · 2019: 47 · 2018: 38 · 2017: 45 · 2016: 44 · 2015: 40 · 2014: 35 · 2013: 26 · 2012: 25
- FWCI
- 21.36
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Cancer Institute (K99CA151293, U54CA126518, P01CA094060, CA 126518, CA94060)
- Topics
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Keywords
- VCAM-1, breast cancer, lung metastasis, macrophages, CD49d, ezrin, PI3K/Akt signaling, TRAIL resistance, apoptosis, juxtacrine signaling
- MeSH terms
- Ezrin, Animals, Breast Neoplasms, Cell Adhesion, Cytoskeletal Proteins, Female, Humans, Leukocytes, Lung Neoplasms, Macrophages, Neoplastic Cells, Circulating, Signal Transduction, Vascular Cell Adhesion Molecule-1, Oncogene Protein v-akt, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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