Background: Brain-derived neurotrophic factor (BDNF) and its receptor TrkB have been reported to be associated with poor prognosis in NB patients. Our previous studies indicated that BDNF activation of TrkB induces chemo-resistance through activating phosphoinositide-3-kinase (PI3K)/Akt pathway. In the present study, we investigated the role of BDNF/TrkB on cell migration and invasion in NB.
Methods: A tetracycline-regulated TrkB-expressing Neuroblastoma cell line (TB3) was used. Scratch wound healing assay, migration and invasion assays were performed when TB3 cells were treated with BDNF or pretreated with the inhibitors for PI3K, MAPK, AKT, and mTOR before BDNF.
Results: TrkB expression was induced in TB3 cells in the absence of tetracycline (TET). Adding BDNF to TrkB-expressing TB3 cells increased the cell migration and invasion. Similar result was not observed in non-TrkB expressing cells in the presence of TET. Pretreatment of TB3 cells with LY294002 (inhibitor for PI3K pathway) or PD98059 (inhibitor for MAPK pathway) before BDNF administration blocked the BDNF/TrkB-induced increase of cell migration and invasion. Furthermore, we found that either AKT inhibitor perifosine or mTOR inhibitor rapamycin could also block the BDNF/TrkB effect on cell migration and invasion.
Conclusions: BDNF activation of TrkB increased NB cell migration and invasion via PI3K/AKT/mTOR pathway or MAPK pathway. Drugs targeting to these pathways or key molecules may be used as potential treatment in NB patients with metastasis.