ABSTRACT
OBJECTIVE: To analyze the capacity of neurotrophic artemin to promote the motility and invasiveness of MIA PaCa-2 pancreatic cancer cells. METHODS: MIA PaCa-2 was cultured in vitro and studied using transwell chambers for motility and invasiveness on treatment with different concentrations of aArtemin or its receptor GFRα3 were also determined. Expression of matrix metalloproteinase-2 (MMP-2) and epithelial cadherin (E-cadherin) was quantified using RT-PCR and Western blotting. RESULTS: MIA PaCa-2 pancreatic cancer cell motility and invasiveness was significantly increased with artemin and its receptor GFRα3 with dose dependence (P<0.01). MMP-2 production was also significantly increased (t=6.35, t=7.32), while E-cadherin was significantly lowered (t=4.27, t=5.61) (P<0.01). CONCLUSION: Artemin and its receptor GFRα3 can promote pancreatic cancer cell motility and invasiveness and contribute to aggressive behavior. The mechanism may be related to increased expression of MMP-2 molecule and down-regulation of E-cadherin expression.
Subject(s)
Cell Movement/physiology , Nerve Growth Factors/metabolism , Nerve Tissue Proteins/metabolism , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/pathology , Blotting, Western , Cadherins/genetics , Cadherins/metabolism , Cell Adhesion , Cell Proliferation , Glial Cell Line-Derived Neurotrophic Factor Receptors/genetics , Glial Cell Line-Derived Neurotrophic Factor Receptors/metabolism , Humans , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 2/metabolism , Neoplasm Invasiveness , Nerve Growth Factors/genetics , Nerve Tissue Proteins/genetics , Pancreatic Neoplasms/genetics , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Tumor Cells, CulturedABSTRACT
OBJECTIVE: To investigate nerve growth factor (beta-NGF) and its receptors expression in human pancreatic ductal adenocarcinoma. METHODS: Expression and distribution of beta-NGF, tyrosine kinase A (TrKA) and P75(NGFR) were detected in operation tissue specimens of pancreatic ductal adenocarcinoma with immunohistochemistry and real-time PCR. Relations of beta-NGF and its receptors with clinical pathological characters, especially nerve invasion were analyzed. RESULTS: beta-NGF and TrKA expression are higher in pancreatic adenocarcinoma than normal pancreas, and the differences are significant (P < 0.01). beta-NGF and TrKA expression are associated with the differentiation grades (DG), lymphatic node metastasis, nerve invasion and surgical pathological stages. Poorer of DG and later stages, more expression of beta-NGF and TrKA. beta-NGF and TrKA expression have positive correlations. beta-NGF, TrKA and P75(NGFR) mRNA expression have significantly increased 3.84, 4.23 and 2.41 times than normal tissues by real-time PCR, respectively. CONCLUSIONS: beta-NGF and TrKA might play potential roles in carcinogenesis for pancreatic cancer, have affinity with clinicopathological characters of pancreatic cancer. beta-NGF and TrKA may have mutual effect in signal transduction leading to perineural invasion of pancreatic carcinoma.
