Pancreatic stellate cells activate Stat3 pathway in pancreatic cancer cells

Background: Pancreatic cancer is characterized by the desmoplastic reaction, which results from the perpetual activation of pancreatic stellate cells (PSCs). There is accumulating evidence that PSCs contribute to the progression of pancreatic cancer. We have previously reported that PSCs induced the proliferation, migration and epithelial-mesenchymal transition (EMT) of pancreatic cancer cells, but the molecular mechanisms responsible for these phenomena remain elusive. Methods: Pancreatic cancer cells were treated with conditioned medium of PSCs (PSC-CM). Activation of Stat3 was assessed by Western blotting using anti-phospho-specific antibodies. Cellular migration was assessed by two chamber assay. Induction of Stat3 target gene CCL2, a chemotactic factor for monocytes, was evaluated by quantitative RT-PCR, Western blotting and ELISA. The expression of CCL2 in human pancreatic cancer tissues was examined by immunohistochemistry. Results: PSC-CM increased the activation of Stat3 in pancreatic cancer cells. NSC75859, an inhibitor of Stat3 pathway, effectively suppressed the cellular migration of pancreatic cancer cells induced by PSC-CM. Similarly, PSC-CM induced CCL2 expression in pancreatic cancer cells, and the induction of CCL2 was inhibited by NSC75859. Pancreatic cancer cells expressed CCL2 in vivo in human pancreatic cancer tissues. Conclusion: PSCs induced the migration and CCL2 expression through the activation of Stat3 pathway. PSCs-induced CCL2 expression might lead to the recruitment of inflammatory cells in the microenvironment of pancreatic cancer.