Integrin alpha2 mediates selective metastasis to the liver.
Integrin alpha2 mediates selective metastasis to the liver.
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DOI：
10.1158/0008-5472.can-09-0315
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发表时间：
2009-09-15
期刊：
影响因子：
11.2
通讯作者：
Schulick RD
中科院分区：
文献类型：
--
作者：
Yoshimura K;Meckel KF;Laird LS;Chia CY;Park JJ;Olino KL;Tsunedomi R;Harada T;Iizuka N;Hazama S;Kato Y;Keller JW;Thompson JM;Chang F;Romer LH;Jain A;Iacobuzio-Donahue C;Oka M;Pardoll DM;Schulick RD
癌症显示器官特异性转移的不同模式。对B16黑色素瘤肝转移亚系与亲本B16-F0的大量细胞膜分子进行比较分析，发现整合素α2的独特上调。整合素α2在肝转移中的直接作用通过高表达与低表达群体、抗体阻断和异位表达的比较来显示。已知整合素α2介导的与IV型胶原的结合（在肝窦中高度暴露）和IV型胶原依赖性黏着斑激酶活化在转移过程中均很重要。分析原发性结直肠癌以及来自个体患者的共存的肝和肺转移表明整合素α2表达有助于人类结直肠癌的肝转移。这些发现将整合素α2定义为赋予肝转移形成的选择性潜力的分子，以及防止其形成的可能靶点。
Cancers display distinct patterns of organ-specific metastasis. Comparative analysis of a broad array of cell membrane molecules on a liver-metastasizing subline of B16 melanoma versus the parental B16-F0 revealed unique up-regulation of integrin α2. The direct role of integrin α2 in hepatic metastasis was shown by comparison of high versus low-expressing populations, antibody blockade, and ectopic expression. Integrin α2–mediated binding to collagen type IV (highly exposed in the liver sinusoids) and collagen type IV–dependent activation of focal adhesion kinase are both known to be important in the metastatic process. Analysis of primary colorectal cancers as well as coexisting liver and lung metastases from individual patients suggests that integrin α2 expression contributes to liver metastasis in human colorectal cancer. These findings define integrin α2 as a molecule conferring selective potential for formation of hepatic metastasis, as well as a possible target to prevent their formation.