Abstract
It has been reported that cancer radiotherapy occasionally results in invasion of survived tumor cells to surrounding tissues. This increased invasiveness seems to be a cellular response to radiation at sub-lethal doses; however, the underlying mechanisms have not been well addressed. To understand the effect of radiation on tumor cell invasion in view of cell motility, we irradiated human glioblastoma cell line A172 (p53 wild) with 3Gy of X-ray, corresponding to approximately 70% of cell survival, and evaluated the number of cells migrated toward laminin, a potent chemoattractant to these cells, through a micropore filter with 8μm pore. The results showed approximately two-fold increase in cell motility by the irradiation, associated with an increased expression of integrin α6β1, a laminin receptor as revealed by flowcytometry using a specific antibody. Furthermore, an increased and sustained phosphorylation of focal adhesion kinase (FAK), a signaling molecule downstream the interaction of integrin and laminin, was observed in irradiated cells. The expression profiles for cell adhesion molecules by microarray technology exhibited the specific upregulation of integrin a subunit and also collagen type 18. Interestingly, all of those cellular responses were suppressed or hardly observed in irradiated A172M (A172 bearing R248W p53 mutant) cells. These results suggest that X-ray irradiation at sub-lethal doses potentiates motility of glioblastoma cells possibly through the mechanisms involving p53-associated upregulation of the integrin-laminin interaction and their downstream signaling pathways.
