Tumor cell alpha3beta1 integrin and vascular laminin-5 mediate pulmonary arrest and metastasis.
Tumor cell alpha3beta1 integrin and vascular laminin-5 mediate pulmonary arrest and metastasis.
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DOI：
10.1083/jcb.200309112
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发表时间：
2004-03-15
影响因子：
7.8
通讯作者：
Muschel, Ruth J
中科院分区：
文献类型：
--
作者：
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
血行转移需要在远处器官中阻止循环肿瘤细胞，但负责的肿瘤细胞表面分子尚未确定。在这里，我们表明，肿瘤细胞α3β1整合素作出了重要贡献，在肺中的逮捕和早期集落形成。这些分析表明，肺停止的发生不仅仅是由于大小的限制，并提出了肿瘤细胞α3β1整合素如何接触其最佳定义的配体层粘连蛋白（LN）-5（基底膜（BM）组分）的问题。进一步的分析表明，LN-5可用于肺血管中预先存在的暴露BM斑块中的肿瘤细胞。通过α3β1整联蛋白与暴露BM中的LN-5相互作用，肺血管系统中肿瘤细胞的早期阻滞为肺转移期间的细胞阻滞提供了分子和结构基础。
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 α3β1 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 α3β1 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 α3β1 integrin with LN-5 in exposed BM provides both a molecular and a structural basis for cell arrest during pulmonary metastasis.