Ionising radiation induces changes associated with epithelial-mesenchymal transdifferentiation and increased cell motility of A549 lung epithelial cells
Ionising radiation induces changes associated with epithelial-mesenchymal transdifferentiation and increased cell motility of A549 lung epithelial cells
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DOI：
10.1016/j.ejca.2007.01.034
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发表时间：
2007-05-01
影响因子：
8.4
通讯作者：
Han, Inn-Oc
中科院分区：
文献类型：
--
作者：
Jung, Jae-Won;Hwang, So-Young;Han, Inn-Oc
放射治疗仍然是晚期肺癌患者的主要治疗选择。然而，辐射对恶性生物行为（例如癌细胞的迁移和转化）的影响仍有待澄清。我们进行了一项体外研究，以探讨辐射诱导的A549人肺癌细胞的形态，粘附和细胞运动的变化。这些变化与上皮-间充质转分化（EMT）相关，似乎与放射诱导的纤维化有关，这是治愈性放射治疗最常见的长期不良反应之一。此外，细胞间粘附的丧失和细胞运动性的增加可能与放疗后相关的转移有关。我们发现，应力纤维和局灶性粘连增加，细胞-细胞连接减少电离辐射的反应。辐射还显著增加了细胞运动性。p38特异性抑制剂SB 203580可抑制辐射促进的A549细胞迁移，而JNK MAPK特异性抑制剂SP 600125可抑制固有的和辐射介导的细胞运动。与此观察结果一致，辐射上调p38 MAPK的磷酸化。目前的癌症治疗方法涉及更密集的放射治疗方案，已被认为与局部或远处转移的发生率较高有关。因此，一部分患者可能受益于放疗与EMT或细胞迁移抑制剂的组合。(c)2007爱思唯尔有限公司保留所有权利。
Radiotherapy remains a major therapeutic option for patients with advanced lung cancer. Nevertheless, the effects of irradiation on malignant biological behaviours (e.g. migration and transformation of cancer cells) have yet to be clarified. We conducted an in vitro study to investigate the radiation-induced alterations including morphology, adhesion, and cell motility of A549 human lung cancer cells. These changes, which are associated with epithelial-mesenchymal transdifferentiation (EMT), seem to be linked to radiation-induced fibrosis, which represents one of the most common long-term adverse effects of curative radiotherapy. In addition, loss of intercellular adhesion and increased cell motility may be involved in post-radiotherapy-associated metastasis. We showed that stress fibres and focal adhesions are increased and that cell-cell junctions are decreased in response to ionising radiation. Radiation also significantly increased cell motility. The p38-specific inhibitor, SB203580, reduced the radiation-promoted migration of A549 cells, whereas SP600125, a JNK MAPK-specific inhibitor, inhibited both inherent and radiation-mediated cell motility. Consistent with this observation, radiation up-regulated the phosphorylation of p38 MAPK. Current approaches to cancer treatment involving more intensive radiotherapy regimens have been suggested to be associated with a higher incidence of local or distant metastasis. Therefore, a subset of patients may benefit from a combination of radiotherapy with inhibitors of EMT or cell migration. (c) 2007 Elsevier Ltd. All rights reserved.