Experimental Study On The Effects Of GDNF On Perineural Invasion Of Pancreatic Carcinoma

Research backgroundIn resent years,the incidence of pancreatic cancer,the most malignant disease in digestive system,has appeared to increase gradually in all over the world.About 40%patients had metastasis at the time of diagnosis,and perineural invasion(PNI) was the most common metasis route for them.The prognostic factors were not uniform in the previous research.It was generally accepted that PNI is responsible for the high recurrence and pain,and was an independent prognostic factor in pancreatic cancer. Previous studies supported that cancer cells invaded the nerves under a plan of lowest resistance in perineurium,spread continuously along perineural space and formed a new metastasis focus in distance.But the exact molecular mechanism of PNI was not fully understood.Recent research put forward the hypothesis that some molecules in the specific perineural microenvironment may prompt proliferation and dissemination of tumor cellsObjectivesTo study the expressions and dependablity of GDNF with the perineural invasion of pancreatic carcinoma and the other biological behaviors in pancreatic cancer tissue. To find the characteristic factors andexplore the molecule mechanisms of PNI in pancreatic carcinomaMethods(1) 46 cases of pancreatic cancer tissue sect serial sections for 6-8 sheets, respectively,for HE staining and immunohistochemical staining.HE sections observed under light microscope to observe the nerve invasion,to distinction between neural and non-neural invasion.(2) Immunochemical EnVision method was adopted to detect the expression of GDNF and NCAM in 46 cases of pancreatic cancer and 12 cases of normal pancreatic tissues. (3) Pancreatic cancer cell strain AsPC-1 was used in this study.AsPC-1 cells cultured in vitro were treated with 10ng/ml,100ng/ml GDNF and the antagonist of the GDNF receptor(RET)--Genistein.The influence of GDNF and Genistein on the mRNA expression of MMP-9 was invested by RT-PCR.Results(1) 46 cases of pancreatic cancer tissue samples were detected out of 21 cases have happened nerve invasion,nerve invasion rate was 45.7 percent happened;(2) The positive expression rates of GDNF in the cancer tissues and normal tissues were 63%and 25%respectively.The different was significant.The positive expression rates of NCAM in the cancer tissues and normal tissues were 66.7%and 32.6%.The different was no-significant(χ~2=3.03,P＞0.05).Positive expression of GDNF was more frequent in perineural invasion group than in non-perineural invasion group,and the different was significant(P＜0.01).In contrast the the positive rate of NCAM was lower inperineural invasion group(P＜0.05)and there was no correlation between them(P＞0.05).Meanwhile expression of them was not associated with tumor differentiation,lymph node metastasis(P＞0.05).(2) GDNF enhanced the mRNA expression of MMP-9.The Genistein could inhibite their effects.Conclusions(1) GDNF and the lack expression of NCAM may enhance the perineural invasion of pancreatic cancer.Detection of them were recommended to precisely find the perineural invasion,derect cancer therapy and predict prognosis.(2) GDNF can en-hance the perineural invasion and metastasis of the pancreatic carci-noma.This effect was related to up-regulated expression of MMP-9.Meanwhile Genistein could inhibite theireffects.