627

BDNF

brain-derived neurotrophic factor;BDNF;brain-derived neurotrophic factor

abrineurin|neurotrophin

11p13

protein-coding

BACKGROUND: Aberrant regulation in the invasion of cancer cells is closely associated with their metastatic potentials. TrkB functions as a receptor tyrosine kinase and is considered to facilitate tumor metastasis. Pyk2 is a non-receptor tyrosine kinase and integrates signals in cell invasion. However, little is known about the expression of TrkB in NSCLC and whether Pyk2 is involved in TrkB-mediated invasion of A549 cells. METHODS: The expression of TrkB was investigated in NSCLC by immunohistochemical staining. Both HBE and A549 cells were treated with BDNF. The expression of TrkB, Pyk2 and ERK phosphorylations were assessed by western blot. Besides, A549 cells were transfected with TrkB-siRNA or Pyk2-siRNA, or treated with ERK inhibitor where indicated. Transwell assay was performed to evaluate cell invasion. RESULTS: 40 cases (66.7%) of NSCLC were found higher expression of TrkB and patients with more TrkB expression had significant metastatic lymph nodes (p = 0.028). BDNF facilitated the invasion of A549 cells and the activations of Pyk2 in Tyr402 and ERK. However, the effects of BDNF were not observed in HBE cells with lower expression of TrkB. In addition, the increased Pyk2 and ERK activities induced by BDNF were significantly inhibited by blocking TrkB expression, so was the invasion of A549 cells. Knockdown studies revealed the essential role of Pyk2 for BDNF-induced cell invasion, since the invasion of A549 cells was abolished by Pyk2-siRNA. The application of ERK inhibitor also showed the suppressed ERK phosphorylation and cell invasion. CONCLUSION: These data indicated that higher expression of TrkB in NSCLC was closely correlated with lymph node metastasis, and BDNF probably via TrkB/Pyk2/ERK promoted the invasion of A549 cells.

OBJECTIVE: This study was to explore the expression and clinicopathologic features of Tyrosine kinase receptors B (TrkB) and its ligand brain-derived neurotrophic factor (BDNF) in nasopharyngeal carcinoma (NPC). METHOD: Immunohistochemistry was adopted to detect the expression level of TrkB and BDNF in NPC patients. RESULT: Both TrkB and BDNF were expressed in NPC as well as in chronic inflammation. The active expression rate of TrkB in NPC was 82.5% (47/57) and BDNF was 52.6% (30/57), both of which were higher than those in chronic inflammation (P < 0.05). The degree of TrkB expression was more marked in T3 + T4, III + IV stage NPC than that in T1 +T2, I + II stage NPC (P < 0.05). TrkB abnormal expression rate of nasopharyngeal carcinoma with lymph node metastasis was higher than that of NPC without lymph node metastasis (P < 0.05). No statistical significance for degrees of TrkB expression in pathologic type grades was found (P > 0.05). There were no statistical significance for degrees of BDNF expression in T stage, clinical stage and lymph node metastasis in NPC (P > 0.05). The expression of TrkB was unrelated to the expression of BDNF (r = 0.049, P > 0.05). CONCLUSION: The high expression rate of TrkB and BDNF maybe plays an important role in development of NPC. It is suggested that TrkB and its ligand BDNF may act as an important index for forecasting the development and metastasis of NPC.

BACKGROUND: Aberrant regulation in the invasion of cancer cells is closely associated with their metastatic potentials. TrkB functions as a receptor tyrosine kinase and is considered to facilitate tumor metastasis. Pyk2 is a non-receptor tyrosine kinase and integrates signals in cell invasion. However, little is known about the expression of TrkB in NSCLC and whether Pyk2 is involved in TrkB-mediated invasion of A549 cells. METHODS: The expression of TrkB was investigated in NSCLC by immunohistochemical staining. Both HBE and A549 cells were treated with BDNF. The expression of TrkB, Pyk2 and ERK phosphorylations were assessed by western blot. Besides, A549 cells were transfected with TrkB-siRNA or Pyk2-siRNA, or treated with ERK inhibitor where indicated. Transwell assay was performed to evaluate cell invasion. RESULTS: 40 cases (66.7%) of NSCLC were found higher expression of TrkB and patients with more TrkB expression had significant metastatic lymph nodes (p = 0.028). BDNF facilitated the invasion of A549 cells and the activations of Pyk2 in Tyr402 and ERK. However, the effects of BDNF were not observed in HBE cells with lower expression of TrkB. In addition, the increased Pyk2 and ERK activities induced by BDNF were significantly inhibited by blocking TrkB expression, so was the invasion of A549 cells. Knockdown studies revealed the essential role of Pyk2 for BDNF-induced cell invasion, since the invasion of A549 cells was abolished by Pyk2-siRNA. The application of ERK inhibitor also showed the suppressed ERK phosphorylation and cell invasion. CONCLUSION: These data indicated that higher expression of TrkB in NSCLC was closely correlated with lymph node metastasis, and BDNF probably via TrkB/Pyk2/ERK promoted the invasion of A549 cells.