Effect of X-ray irradiation on tumor metastasis

该项目的目的是更好地了解X射线照射增强肿瘤侵袭的细胞和分子机制，特别是细胞黏附分子与细胞外基质相互作用所产生的细胞迁移和细胞内信号转导。迁移实验表明，胶质瘤细胞系A172向层粘连蛋白(LM)定向迁移，通过微孔膜过滤器对迁移的细胞数量进行了定量。细胞暴露在3GyX射线下，细胞存活率下降到未照射细胞的约70%，导致与LM结合的整合素-β1亚单位表达增加，导致细胞迁移增强。位于R248W的突变型p53细胞株A172M经X射线照射后，细胞的迁移率和整合素-β-1的表达没有发生任何变化。粘着斑激酶(FAK)的磷酸化证实了辐射增强整合素与LM的相互作用。此外，FAK下游的信号分子之一、MAPK成员ERK1/2在X射线照射后也被磷酸化。这些发现表明，亚致死剂量的X射线照射至少部分地通过促进LM和整合素的相互作用来诱导肿瘤侵袭，从而导致细胞信号的增强。此外，P53可能在该信号通路中起一定作用。

The aim of this project was to better understand the cellular and molecular mechanisms underlying enhanced tumor invasion by X-ray irradiation, especially focusing on cell mobility and intracellular signaling originated from the interaction of cell adherence molecules with extracellular matirix. The glioma cell line A172 exhibited directed migration to laminin (LM) as revealed by the migration assay which quantitate the number of migrated cells through a micropore membrane filter. Exposure of the cells to 3Gy of X ray, which decreases cell survival to approximately 70% of unirradiated, resulted in enhanced migration associated with elevated expression of integrin-β1 subunit that binds to LM. A172M cells, a p53 mutant cell line at R248W, did not show any changes in mobility and integrin-β1 expression following X-ray irradiation. Tie enhanced interaction of integrin and LM by the irradiation was confirmed by the phosphorylations of focal adhesion kinase (FAK). Furthermore, ERK1/2, a member of MAPK and one of the signaling molecules downstream of FAK, was also phosphorylated after X-ray irradiation. These findings suggests that X-ray irradiation at a sublethal dose induces tumor invasion by, at least in part, promoting the interaction of LM and integrins which leads to elevated cellular signaling. Furthermore, p53 might play some part in that signal pathways.