Role of α(5)β(1) Integrin Up-regulation in Radiation-Induced Invasion by Human Pancreatic Cancer Cells.

RADIOTHERAPY IS USED IN THE MANAGEMENT OF PANCREATIC CANCER BECAUSE OF ITS HIGH PROPENSITY FOR LOCOREGIONAL RELAPSE

one third of patients succumb to localized disease. Thus, strategies to improve the efficacy of radiotherapy in pancreatic cancer are important to pursue. We used naturally serum-free, selectively permeable basement membranes and confocal microscopy of fluorescent antibody-stained human Panc-1, MiaPaCa-2, and BxPC-3 pancreatic cancer cell lines to investigate the effects of ionizing radiation on α(5)β(1) integrin fibronectin receptor expression and on α(5)β(1)-mediated invasion. We report that radiation rapidly induces pancreatic cancer cell invasion, and that radiation-induced invasion is caused by up-regulation of α(5)β(1) integrin fibronectin receptors by transcriptional and/or postendocytic recycling mechanisms. We also report that radiation causes α(5)β(1) up-regulation in Panc-1, MiaPaCa-2, and BxPC-3 tumor xenografts and that upregulated α(5)β(1) colocalizes with upregulated early or late endosomes in Panc-1 or BxPC-3 tumors, respectively, although it may colocalize significantly with both endosome types in MiaPaCa-2 tumors. Our results suggest that systemic inhibition of α(5)β(1)-mediated invasion might be an effective way to reduce radiation-induced pancreatic cancer cell invasion, thereby improving the efficacy of radiotherapy.