Perineural invasion is a prominent characteristic of pancreatic cancer. Pancreatic cancer has an extremely high incidence of perineural invasion which has been associated with poor survival. Early studies mostly focus on the interaction between cancer cells and nerves. Recently, the effect of pancreatic stellate cells in progression of pancreatic cancer has been paid more attention. Both in vitro studies and in vivo ones revealed that pancreatic stellate cells can enhance the proliferation, migration and invasion of pancreatic cancer cells. Pancreatic stellate cells can also regulate the expression and effect of molecules involved in perineural invasion. In addition, pancreatic stellate cells seems to associated with the generation of neuronal plasticity in pancreatic cancer. Herein the hypothesis that pancreatic stellate cells play a potential role in promote the perineural invasion in pancreatic cancer through three mechanisms. One is that pancreatic stellate cells enhance the proliferation, migration and invasion directly through releasing a variety of stimuli and providing a suitable microenvironment. Pancreatic stellate cells also regulate the expression and effects of molecules involved in perineural invasion such as nerve growth factor. Another is that pancreatic stellate cells induce neuronal plasticity, which makes nerves more vulnerable to be invaded. We can conclude that pancreatic stellate cells play a central role in regulating the perineural invasion process by producing different effects on cancer cells and nerve. To inhibit the activity of pancreatic stellate cells or block the interaction between pancreatic stellate cells and cancer cells or nerve tissue might reduce the perineural invasion in pancreatic cancer.
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