Clarification of control mechanisms for lever metastasis and nerve invasion in pancreatic cancer

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We previously reported that the neurotrophic factor GDNF has an important role in the invasive capability of pancreatic cancer cells. Furthermore, we confirmed that the integrins have a critical role for invasive and metastatic potential of pancreatic cancer cell lines. The aims of this study was to identify the role of GDNF for pancreatic cancer cell adhesive and invasive capabilities.We report the results that we acquired till now as follows.1. GDNF significantly activated ERK-1/2 and PI3-K signaling pathways, furthermore, the activation of transcription factor NF-kB was observed.2. GDNF significantly enhanced the expression of integrin subunits involved in adhesive and invasive capabilities of pancreatic cancer cells.3. GDNF correlated with the activation of ERK-1/2 signaling pathways in pancreatic cancer cells and these enhancements can be inhibited by MEK-1 inhibitor.4. Invasive potential of pancreatic cancer cells was also regulated by NF-kB activation via GDNF stimulation. Furthermore, NF-kB inhibitor had an important role in the inhibition of neural invasion in human pancreatic cancer cells.In this study, we proved the signaling pathways involved in neural invasion in human pancreatic cancer cells, and our results suggested that the control of these signaling pathways contributes to the improvement of cure rate for pancreatic cancer.