期刊
TRANSLATIONAL ONCOLOGY
卷 4, 期 5, 页码 282-292出版社
NEOPLASIA PRESS
DOI: 10.1593/tlo.11133
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资金
- National Institutes of Health [R01 CA119007, R03 CA 127050]
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 alpha(5)beta(1) integrin fibronectin receptor expression and on alpha(5)beta(1)-mediated invasion. We report that radiation rapidly induces pancreatic cancer cell invasion, and that radiation-induced invasion is caused by up-regulation of alpha(5)beta(1) integrin fibronectin receptors by transcriptional and/or postendocytic recycling mechanisms. We also report that radiation causes alpha(5)beta(1) up-regulation in Panc-1, MiaPaCa-2, and BxPC-3 tumor xenografts and that upregulated alpha(5)beta(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 alpha(5)beta(1)-mediated invasion might be an effective way to reduce radiation-induced pancreatic cancer cell invasion, thereby improving the efficacy of radiotherapy.
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