Radiation promotes epithelial-to-mesenchymal transition and invasion of pancreatic cancer cell by activating carcinoma-associated fibroblasts.

The tumor microenvironment is of crucial importance affecting treatment and prognosis. High degree of carcinoma-associated fibroblast (CAF) infiltration occurs in pancreatic cancer, though its effect on radiotherapy remains unclear. In this study, we demonstrated that radiation enhanced the migration- and invasion-promoting capacity of CAFs both in vitro and in vivo in a lung metastasis model. Radiation exposure increased the expression of CXCL12 by CAFs. CAF-derived CXCL12 promoted tumor cell EMT and invasion directly, acting through CXCR4 on pancreatic cancer cells. In addition, we showed that CXCL12-CXCR4 signaling promoted pancreatic cancer cell EMT and invasion by activating the P38 pathway. Therefore, our study concluded that radiation promoted pancreatic cancer cell invasion and EMT by activating CAFs, while inhibiting the CXCL12/CXCR4 interaction between pancreatic cancer cells and CAFs could potentially attenuate tumor cell invasion induced by radiation, which provides an opportunity for the development of novel therapeutic targets to improve the prognosis for human pancreatic cancer treated with radiation therapy.