BDNF Promote Neural Invasion and Resistance to Anoikis of ACC

Objectives: The aim of this study was to evaluate the role of TrkB-BDNF (TrkB: tyrosine kinase receptor; BDNF: brain-derived neurotrophic factor) pathway in the Perineural Invasion and resistance to anoikis of Adenoid Cystic Carcinoma (ACC) . Methods: 35 cases of primary ACC samples of the head and neck were immunostained to analyze BDNF and TrkB protein expression. 15 normal parotid glands and 10 acinic cell carcinoma tissue samples were used as control. RT-PCR and Western-Blot were carried on Adenoid Cystic Carcinoma cell line including ACC-2 and ACC-M to analysis the mRNA and protein expression of BDNF and TrkB. Suspension culture system were used to simulate the environment of anoikis in vitro. Clone formation rate, FCM and MTT were used to evaluate the survival ability and anoikis resistance of ACC cell line when exposed to BDNF. Results: BDNF and TrkB were present in all 35 cases of ACC samples. Compared with 20 samples without perineural invasion, 20 samples with perineural Invasion showed higher expression of TrkB (p<0.05). RT-PCR and Western-Blot results verified that BDNF and TrkB were expression in both ACC-2 and ACC-M. No difference was found between ACC-2 and ACC-M (p>0.05). With Suspension culture system we found both ACC-2 and ACC-M had the ability of anoikis resistance and this kind of ability could be improved when exposed to BDNF. Conclusion: TrkB-BDNF pathway may play an important role in Perineural Invasion and resistance to anoikis of Adenoid Cystic Carcinoma. Blocking of TrkB-BDNF pathway may be considered as a gene therapy method to treat ACC.