Clarification of Nerve Invasion System in Pancreatic Cancer

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We report the results that we acquired till now as follows.1.The expression of GDNF and RET in the intra-and extra-pancreatic nerve plexus was observed by immunohistochemical analysis in resected specimens. It was also proved that pancreatic cancer cells and peri-pancreatic tissues excrete GDNF.2.The role of NF-κB in signaling pathway via GDNF-RET was investigated.(1)MG-132, proteasome inhibior, inhibited the proliferation of pancreatic cancer cells in dose-dependent manner.(2)The invasion cell number and the NF-κB activity were increased by GDNF stimulation. But in the presence of MG132 or I-κB activity were significantly suppressed and remained suppressed after GDNF stimulation.(3)GDNF upregulates the expression and enzymatic activity of MMP-9, and this may promote pancreatic cancer invasion to the extracellular matrixes.