Tumor cell alpha3beta1 integrin and vascular laminin-5 mediate pulmonary arrest and metastasis.

Wang H, Fu W, Im JH, Zhou Z, Santoro SA, Iyer V, DiPersio CM, Yu QC, Quaranta V, Al-Mehdi A, Muschel RJ
J Cell Biol. 2004 164 (6): 935-41

PMID: 15024036 · PMCID: PMC2172296 · DOI:10.1083/jcb.200309112

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 alpha3beta1 integrin 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 alpha3beta1 integrin 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 alpha3beta1 integrin with LN-5 in exposed BM provides both a molecular and a structural basis for cell arrest during pulmonary metastasis.

MeSH Terms (17)

Animals Antibodies Basement Membrane Blood Vessels Cell Adhesion Cell Adhesion Molecules Cell Line, Tumor Humans Integrin alpha3 Integrin beta1 Ligands Lung Mice Neoplasm Invasiveness Neoplasm Metastasis Neoplasms Rats

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