Tumor cell alpha3beta1 integrin and vascular laminin-5 mediate pulmonary arrest and metastasis |
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| 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 |
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| Affiliation: | Dept. of Pathology, Rm. 916D ARC, Children's Hospital of Philadelphia, 3615 Civic Center Blvd., Philadelphia, PA 19104, USA. |
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| 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. |
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| Keywords: | metastasis tumor cell integrin laminin vessel |
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