PMID- 26530352 OWN - NLM STAT- MEDLINE DCOM- 20161006 LR - 20220311 IS - 1791-2431 (Electronic) IS - 1021-335X (Linking) VI - 35 IP - 1 DP - 2016 Jan TI - Schwann cells promote EMT and the Schwann-like differentiation of salivary adenoid cystic carcinoma cells via the BDNF/TrkB axis. PG - 427-35 LID - 10.3892/or.2015.4366 [doi] AB - 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. FAU - Shan, Chun AU - Shan C AD - 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. FAU - Wei, Jianhua AU - Wei J AD - 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. FAU - Hou, Rui AU - Hou R AD - 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. FAU - Wu, Baolei AU - Wu B AD - 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. FAU - Yang, Zihui AU - Yang Z AD - 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. FAU - Wang, Lei AU - Wang L AD - 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. FAU - Lei, Delin AU - Lei D AD - 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. FAU - Yang, Xinjie AU - Yang X AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151030 PL - Greece TA - Oncol Rep JT - Oncology reports JID - 9422756 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Membrane Glycoproteins) RN - 7171WSG8A2 (BDNF protein, human) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - EC 2.7.10.1 (Receptor, trkB) RN - EC 2.7.10.1 (tropomyosin-related kinase-B, human) SB - IM MH - Brain-Derived Neurotrophic Factor/*genetics/metabolism MH - Carcinoma, Adenoid Cystic/genetics/metabolism/*pathology MH - Cell Differentiation MH - Cell Line, Tumor MH - Cell Movement MH - Coculture Techniques MH - *Epithelial-Mesenchymal Transition MH - Gene Expression Regulation, Neoplastic MH - Humans MH - Membrane Glycoproteins/*genetics/metabolism MH - Neoplasm Invasiveness MH - Protein-Tyrosine Kinases/*genetics/metabolism MH - Receptor, trkB MH - Salivary Gland Neoplasms/genetics/metabolism/*pathology MH - Schwann Cells/*cytology MH - Signal Transduction EDAT- 2015/11/05 06:00 MHDA- 2016/10/08 06:00 CRDT- 2015/11/05 06:00 PHST- 2015/08/02 00:00 [received] PHST- 2015/09/23 00:00 [accepted] PHST- 2015/11/05 06:00 [entrez] PHST- 2015/11/05 06:00 [pubmed] PHST- 2016/10/08 06:00 [medline] AID - 10.3892/or.2015.4366 [doi] PST - ppublish SO - Oncol Rep. 2016 Jan;35(1):427-35. doi: 10.3892/or.2015.4366. Epub 2015 Oct 30.