Exploration Of The Function Of The Glial Cell Line-derived Neurotrophic Factor In Pancreatic Carcinoma Neural Invasion

Pancreatic cancer is one of the most malignant tumors,which has very poor prognosis. Only 10%-15%of the patients have chance to receive operation,5%-7.5%have chance to accept complete resection.Even after resection,it has high incidence to reccur.Pancreatic cancer has an unusual tendency to invade into and around neural tissues even in the early stages of the disease.The neural tissue surrounding the pancreas is capable of producing a variety of humoral factors or adhesion molecules factors which can activate pancreatic cancers and facilitate their extension along nerves.One of them,the socalledglial cell line-derived neurotrophic factor(GDNF)has been implicated in perineural invasion of pancreatic cancer cell.Objeetivel.To investigate the relations between the expressions of GDNF,the related receptors and MMP-9 and neural invasion in the orthotopic animal model of pancreatic cancer in nude mouse.2.To investigate the effect of GDNF in pancreatic cancer cell proliferation and invasion.3.To investigate whether GDNF regulates the expression of matrix metalloproteinase-9(MMP-9)mRNA and protein in human pancreatic cancer cells.Methods 1.We set up an orthotopic animal model for pancreatic cancer and use immunohistochemical technique to nvestigate the relations between the expressions of GDNF,the related receptors and MMP-9 and neural invasion.2.Make use of cell counting,MTT and flow cytometry to investigate whether the neurotrophic factor GDNF contributes to the development of the malignant phenotype of pancreatic carcinoma cells by stimulating proliferation or chemotaxis.3 Make use of RT-PC Rand enzyme-linked immunosorbent assay to investigate the effect of GDNF on MMP-9 mRNA and protein expression.Results 1.Panc,reatic cancer has an unusual tendency to invade into and around neural tissues even in the early stages of the disease with or without other metastasis.The expressions of GDNF and it's receptor RET were correlated with neural invasion.2.Cells were exposed to incremental concentrations of human recombinant GDNF(0-120 ng/mL).We found that the proliferation of pancreatic cancer cell was stimulated and the counting of cells invasion was increased by GDNF in a dose-dependent manner.3.After adding GDNF to pancreatic cancer cell line,we found that GDNF could upregulate MMP-9 mRNA expression and stimulate MMP-9 protein expression.Conclusions: 1.Pancreatic cancer has an unusual tendency to invade into and around neural tissues even in the early stages of the disease.The expressions of GDNF and it's receptor RET were correlated with neural invasion.2.GDNF can stimulate the proliferation and invasion of pancreatic cancer cell.3.GDNF can upregulate MMP-9 mRNA expression and stimulate MMP-9 protein expression,then it can stimulate cell invasion in pancreatic cancer cell.