Effect of X-ray irradiation on tumor metastasis

本项目的目的是更好地理解X射线照射增强肿瘤侵袭的细胞和分子机制，特别是关注细胞移动性和源自细胞粘附分子与细胞外基质相互作用的细胞内信号传导。胶质瘤细胞系A172表现出定向迁移到层粘连蛋白（LM），如通过迁移试验所揭示的，该迁移试验定量通过滤膜的迁移细胞的数量。将细胞暴露于3Gy的X射线，其使细胞存活率降低至未照射的约70%，导致与结合LM的整合素β1亚基的表达升高相关的迁移增强。A172 M细胞是一种p53突变的细胞系，在X射线照射后，其迁移率和整合素β1表达没有任何变化。粘着斑激酶（FAK）的磷酸化证实了辐射增强了整合素与LM的相互作用。此外，MAPK的成员和FAK下游的信号分子之一的ERK 1/2在X射线照射后也被磷酸化。这些发现表明，X射线照射在亚致死剂量诱导肿瘤侵袭，至少部分地，促进LM和整合素的相互作用，导致细胞信号的升高。此外，p53可能在该信号通路中发挥一定作用。

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.