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

Abstract

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.

• Authors: Hui Wang, Weili Fu, Jae Hong Im, Zengyi Zhou, Samuel A Santoro, Vandana Iyer, C Mike DiPersio, Qian-Chun Yu, Vito Quaranta, Abu Al-Mehdi, Ruth J Muschel
• Journal: The Journal of cell biology (J Cell Biol) Vol. 164 Issue 6 Pg. 935-41 (Mar 15 2004) ISSN: 0021-9525 [Print] United States
• PMID: 15024036 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies
• Cell Adhesion Molecules
• Integrin alpha3
• Integrin beta1
• Ligands
• kalinin

Topics

• Animals
• Antibodies (metabolism)
• Basement Membrane (metabolism, ultrastructure)
• Blood Vessels (anatomy & histology, metabolism)
• Cell Adhesion
• Cell Adhesion Molecules (metabolism)
• Cell Line, Tumor
• Humans
• Integrin alpha3 (immunology, metabolism)
• Integrin beta1 (metabolism)
• Ligands
• Lung (blood supply, metabolism, pathology)
• Mice
• Neoplasm Invasiveness
• Neoplasm Metastasis
• Neoplasms (metabolism)
• Rats