The CCL5/CCR5 Chemotactic Pathway Promotes Perineural Invasion in Salivary Adenoid Cystic Carcinoma

Publication date: Available online 20 February 2018
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Tao Gao, Zhiyuan Shen, Chao Ma, Yun Li, Xiangfeng Kang, Moyi Sun
PurposePerineural invasion (PNI) is a hallmark of salivary adenoid cystic carcinoma (SACC) and represents an important risk factor for local recurrence and poor survival. However, the mechanism of PNI has yet to be explored. In this study, we sought to examine the CCL5-CCR5 ligand-receptor interaction between nerves and salivary adenoid cystic carcinoma cells.Materials and methodsCCL5/CCR5 expression was determined by immunohistochemistry in SACC tissue specimens. Correlations between CCL5/CCR5 expression and clinicopathologic features were investigated. Dorsal root ganglia (DRG) and SACC cells cocultured in vitro were used to evaluate the effects of CCL5/CCR5 on PNI progression and pathogenesis.ResultsCCR5 expression was significantly elevated in SACC tissues and associated with distant metastasis, perineural invasion, and TNM grade (P<0.05). Dorsal root ganglia (DRG) and SACC cells cocultured in vitro showed that the activation of the CCL5/CCR5 axis significantly increased SACC cells invasion and promoted the outgrowth of the DRG. SACC cell lines expressing CCR5 migrated in response to CCL5 derived from DRG, eventually leading to PNI. Most importantly, further study showed that blocking of CCL5 or CCR5 effectively inhibited the invasive capacity and PNI activity of SACC cells (P<0.05).ConclusionsOur study suggests a pivotal role of CCL5/CCR5 axis in tumor-nerve interactions during PNI of SACC. The CCL5/CCR5 pathway may prove to be an attractive new target for the treatment of SACC with PNI.



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