Integrin β1-dependent invasive migration of irradiation-tolerant human lung adenocarcinoma cells in 3D collagen matrix
Integrin β1-dependent invasive migration of irradiation-tolerant human lung adenocarcinoma cells in 3D collagen matrix
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DOI：
10.1016/j.bbrc.2010.04.150
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发表时间：
2010-06-04
影响因子：
3.1
通讯作者：
Nishioka, Takeshi
中科院分区：
文献类型：
--
作者：
Ishihara, Seiichiro;Haga, Hisashi;Nishioka, Takeshi
放射治疗是治疗各种恶性肿瘤的有效方法之一。然而，由于耐受细胞的高转移能力，在照射后耐受细胞的出现仍然是有问题的，有时表明预后不良。在这项研究中，我们发现，亚克隆的人肺腺癌细胞（A549 P-3），是辐射耐受性表明在体外高侵袭活性，并表现出整合素β 1活性依赖性迁移模式。胶原凝胶覆盖法显示，大多数A549 P-3细胞呈圆形，迁移活性低，而相当数量的A549 P-3 IR细胞则呈梭形，迁移率高。阻断整合素β 1活性降低了A549 P-3 IR细胞的迁移率，并改变了细胞形态，使其呈圆形。这些结果表明，A549 P-3细胞辐射存活获得高度侵袭性的整合素β 1依赖性表型，整合素β 1可能是一个潜在的有效的治疗靶点与放射治疗相结合。(C)2010年爱思唯尔公司All rights reserved.
Radiotherapy is one of the effective therapies used for treating various malignant tumors. However, the emergence of tolerant cells after irradiation remains problematic due to their high metastatic ability, sometimes indicative of poor prognosis. In this study, we showed that subcloned human lung adenocarcinoma cells (A549P-3) that are irradiation-tolerant indicate high invasive activity in vitro, and exhibit an integrin beta 1 activity-dependent migratory pattern. In collagen gel overlay assay, majority of the A549P-3 cells displayed round morphology and low migration activity, whereas a considerable number of A549P-3IR cells surviving irradiation displayed a spindle morphology and high migration rate. Blocking integrin beta 1 activity reduced the migration rate of A549P-3IR cells and altered the cell morphology allowing them to assume a round shape. These results suggest that the A549P-3 cells surviving irradiation acquire a highly invasive integrin beta 1-dependent phenotype, and integrin beta 1 might be a potentially effective therapeutic target in combination with radiotherapy. (C) 2010 Elsevier Inc. All rights reserved.