Ionizing radiation (IR) is commonly used for
cancer therapy, however, its potential influence on
cancer metastatic potential remains controversial. In this study, we elucidated the role of
integrins in regulation of IR-altered adhesion between
breast cancer cells and extracellular matrix (ECM)
proteins, which is a key step in the initial phase of
metastasis. Our data suggest that the extent of effect that ionizing radiation had on cell adhesion depended on the genetic background of the
breast cancer cells. Ionizing radiation was a better adhesion inducer for p53-mutated cells, such as MDA-MB-231 cells, than for p53 wild-type cells, such as MCF-7 cells. While IR-induced adhesions between MDA-MB-231 cells to
fibronectin,
laminin,
collagen I and
collagen IV, only blocking of the adhesion between α5β1
integrin and
fibronectin using anti-α5β1
integrin antibody could completely inhibit the radiation-induced adhesion of the cells. A soluble
Arg-Gly-Asp peptide, the binding motif for
fibronectin binding
integrins, could also reduce the adhesion of the cells to
fibronectin with or without ionizing radiation exposure. The inhibition of the cell-
fibronectin interaction also affected, but did not always correlate with, transwell migration of the
cancer cells. In addition, our data showed that the total expression of α5
integrin and surface expression of α5β1
integrin were increased in the cells treated with ionizing radiation. The increased surface expression of α5β1
integrin, along with the adhesion between the cells and
fibronectin, could be inhibited by both
ataxia telangiectasia mutated (ATM) and Rad3-related (ATR)
kinase inhibitors. These results suggested that ATM/ATR-mediated surface expression of α5β1
integrin might play a central role in regulation of ionizing radiation-altered adhesion.