Tumor Cell α3β1Integrin and Vascular Laminin-5 Mediate Pulmonary Arrest and Metastasis

Arrest of circulating tumor cells in distant organs is required for hematogenous metastasis, but the tumor cell surface molecules responsible have not been identified. Here, we show that the tumor cell α3β1integrin makes an important contribution to arrest in the lung and to early colony formation....

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Bibliographic Details
Published in:The Journal of cell biology 2004-03, Vol.164 (6), p.935-941
Main Authors: Wang, Hui, Fu, Weili, Im, Jae Hong, Zhou, Zengyi, Santoro, Samuel A., Iyer, Vandana, DiPersio, C. Mike, Yu, Qian-Chun, Quaranta, Vito, Al-Mehdi, Abu, Muschel, Ruth J.
Format: Article
Language:English
Subjects:
Antibodies
Blocking antibodies
Cell lines
Cells
Endothelial cells
Integrins
K562 cells
Lungs
Metastasis
Tumors
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Summary:Arrest of circulating tumor cells in distant organs is required for hematogenous metastasis, but the tumor cell surface molecules responsible have not been identified. Here, we show that the tumor cell α3β1integrin makes an important contribution to arrest in the lung and to early colony formation. These analyses indicated that pulmonary arrest does not occur merely due to size restriction, and raised the question of how the tumor cell α3β1integrin contacts its best-defined ligand, laminin (LN)-5, a basement membrane (BM) component. Further analyses revealed that LN-5 is available to the tumor cell in preexisting patches of exposed BM in the pulmonary vasculature. The early arrest of tumor cells in the pulmonary vasculature through interaction of α3β1integrin with LN-5 in exposed BM provides both a molecular and a structural basis for cell arrest during pulmonary metastasis.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.200309112