title: The CCL5/CCR5 axis contributes to the perineural invasion of human salivary adenoid cystic carcinoma.
abstract: Salivary adenoid cystic carcinoma (SACC) has a unique tendency for perineural invasion (PNI), which results in tumor recurrence and poor prognosis. Recent studies have shown that the chemokine CCL5 and its receptor CCR5 play important roles in tumor invasion and metastasis. However, the role of the CCL5/CCR5 axis in the PNI of SACC has not been studied to date. In the present study, we evaluated the expression of CCL5 and CCR5 in SACC cases and nerve tissues, and performed a series of in vitro assays with the SACC cell line, SACC-83, to indicate the role of the CCL5/CCR5 axis in the PNI of SACC. We found that CCL5 (35.9%; 23/64) and CCR5 (70.3%; 45/64) were positively expressed in SACC cases, and the expression of CCR5 was significantly associated with the PNI of SACC (P<0.05). We also found that SACC-83 cells expressed the functional receptor, CCR5, for the chemokine CCL5, as demonstrated by calcium mobilization and actin polymerization assays. Furthermore, we found that exogenous CCL5 significantly facilitated the migration, invasion and PNI activity of SACC-83 cells in vitro (P<0.05). Further study showed that the CCR5 inhibitor (maraviroc) effectively blocked the migration, invasion and PNI activity of SACC-83 cells with or without CCL5 stimulation (P<0.05). These results indicate that the CCL5/CCR5 axis plays a critical role in the PNI of SACC, and that antagonists against CCR5 may be an effective anti-PNI agent for SACC therapy.
authors: Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors: Zhiyuan
authors: Z
authors: Shen
authors: Department of Pediatric Dentistry, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors: Tianyi
authors: T
authors: Li
authors: Department of Oral Medicine, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors: Da
authors: D
authors: Chen
authors: Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors: Sen
authors: S
authors: Jia
authors: Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors: Xiangming
authors: X
authors: Yang
authors: Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors: Liang
authors: L
authors: Liang
authors: Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors: Juan
authors: J
authors: Chai
authors: Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors: Xiaobing
authors: X
authors: Cheng
authors: Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors: Xinjie
authors: X
authors: Yang
authors: Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors: Moyi
authors: M
authors: Sun
mesh_terms: D065100:CCR5 Receptor Antagonists; D003528:Carcinoma, Adenoid Cystic / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D018946:Chemokine CCL5 / Q000378:metabolism* / Q000494:pharmacology; D003510:Cyclohexanes / Q000494:pharmacology; D006801:Humans; D000077592:Maraviroc; D009361:Neoplasm Invasiveness / Q000473:pathology* / Q000517:prevention & control; D009362:Neoplasm Metastasis / Q000473:pathology; D009364:Neoplasm Recurrence, Local; D010525:Peripheral Nerves / Q000473:pathology; D019713:Receptors, CCR5 / Q000378:metabolism*; D012468:Salivary Gland Neoplasms / Q000473:pathology*; D014230:Triazoles / Q000494:pharmacology
chemical_list: C483024:CCL5 protein, human; D065100:CCR5 Receptor Antagonists; C584933:CCR5 protein, human; D018946:Chemokine CCL5; D003510:Cyclohexanes; D019713:Receptors, CCR5; D014230:Triazoles; D000077592:Maraviroc