Association between breast cancer cell migration and radiosensitivity .

The aim of the present study was to examine the association between the migration of breast cancer cells and radiosensitivity by establishing a breast cancer cell model with different migratory capacities. Transwell chambers in a 24-well plate were used to separate MDA-MB-231 and ZR-7530 cells and to establish cell models with different migratory capacities. Subsequently, the radiosensitivity of the cell models was measured using a radiation clone formation assay. Furthermore, differential gene expression was determined using gene microarray analysis. The protein expression levels of the differentially expressed genes (DEGs) were assessed using western blot analysis. From each parental cell line, a pair of daughter cell lines were established in with differing migratory abilities. These daughter cell lines were named MDA-MB-231 UP-10 (231 UP-10), MDA-MB-231 Down-10 (231 Down-10), ZR-75-30 UP-10 (7530 UP-10) and ZR-75-30 Down-10 (7530 Down-10). Radiation clone formation assays revealed that the cell lines with increased migratory abilities (231 Down-10 and 7530 Down-10) demonstrated higher radio-resistance compared with the cell lines with decreased migratory abilities (231 UP-10 and 7530 UP-10). Gene microarrays identified numerous DEGs between the pairs of UP and Down cell lines. A focus was placed on genes associated with cell adhesion and it was identified that phosphorylated Fak and phosphorylated EGFR expression levels were increased in 231 Down-10 and 7530 Down-10 cells, compared with the 231 UP-10 and 7530 UP-10 cells. Other genes including ZO-1, FN1 and SOX9 expression were also increased in the 231 Down-10 and 7530 Down-10 cells compared with 231 UP-10 and 7530 UP-10 cells. Cell lines with increased migratory capacities may be more radio-resistant compared with cell lines with a decreased migratory capabilities. The mechanism may be associated with changes in the expression of cell adhesion molecules and epithelial-mesenchymal transition (EMT). Therapeutic strategies targeting cell adhesion or EMT may increase the radiation sensitivity of breast cancer cells, in addition to improving the effect of radiation therapy.