Schwann cells promote EMT and the Schwann-like differentiation of salivary adenoid cystic carcinoma cells via the BDNF/TrkB axis

Shan,Chun; Wei,Jianhua; Hou,Rui; Wu,Baolei; Yang,Zihui; Wang,Lei; Lei,Delin; Yang,Xinjie

doi:10.3892/or.2015.4366

Schwann cells promote EMT and the Schwann-like differentiation of salivary adenoid cystic carcinoma cells via the BDNF/TrkB axis

Authors:
- Chun Shan
- Jianhua Wei
- Rui Hou
- Baolei Wu
- Zihui Yang
- Lei Wang
- Delin Lei
- Xinjie Yang
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Affiliations: State Key Laboratory of Military Stomatology, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China
Published online on: October 30, 2015 https://doi.org/10.3892/or.2015.4366
Pages: 427-435

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Abstract

Perineural invasion (PNI) is a striking biological behavior observed in salivary adenoid cystic carcinoma (SACC). The present study was designed to establish a co‑culture model of SACC cells with Schwann cells (SCs), and then study epithelial-mesenchymal transition (EMT) and the Schwann‑like differentiation of SACC cells to investigate the likely molecular mechanism of PNI. The co‑culture models of SCs with tumor cells (SACC‑83, SACC‑LM and MEC‑1) were established using a Transwell system. An elevated concentration of brain‑derived neurotrophic factor (BDNF) was detected by ELISA assay in the co‑cultured medium of the SACC‑83 group and SACC‑LM group rather than the MEC‑1 group. The EMT process and Schwann‑like differentiation in SACC‑83 cells were analyzed by RT‑PCR, western blotting, immunofluorescence, photography, and migration and perineural invasion assays. The SACC‑83 cells under the co‑culture condition with SCs changed to a mesenchymal morphology and had higher migration and invasion capabilities compared with the solely cultured SACC‑83 cells, accompanied by the downregulation of E‑cadherin and upregulation of N‑cadherin and vimentin. The co‑cultured SACC‑83 cells also developed Schwann‑like differentiation with increased expression of SC markers, S100A4 and GFAP. However, inhibition of tropomyosin‑related kinase B (TrkB) by K252a markedly blocked these effects. Additionally, the expression and correlation of TrkB, E‑cadherin and S100A4 were analyzed by immunohistochemistry in 187 primary SACC cases. The levels of TrkB and S100A4 expression were both positively associated with PNI in the SACC cases, while E‑cadherin expression was negatively associated with PNI. Elevated expression of TrkB was significantly correlated with the downregulated expression of E‑cadherin and the upregulated expression of S100A4 in the SACC cases. Our results suggest that SCs play a pivotal role in the PNI process by inducing the EMT process and the Schwann‑like differentiation of SACC cells via the BDNF/TrkB axis. Interruption of the interreaction between SACC cells and SCs by targeting the BDNF/TrkB axis may be a potential strategy for anti-PNI therapy in SACC.

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