Abstract C20: CXCR4 antagonist inhibits perineural invasion of adenoid cystic carcinoma in preclinical murine model

Abstract

Abstract Background. Perineural invasion is a characteristic feature of salivary adenoid cystic carcinoma (ACC). Expression of CXCR4 is also a characteristic feature of ACC which distinguishes it from other non-neurotropic head and neck cancers. Therefore, CXCR4 may play a role in the perineural invasion of ACC. In this study, we aimed to demonstrate CXCR4 expression in ACC, to identify its association with perineural invasion, and to investigate the impact of CXCR4 inhibitor in vitro and in a murine perineural invasion model. Materials & Methods. Expression of CXCR4 was assessed in ACC cell lines and in human tissue. The effect of gene knockdown using siRNA and a specific blocker of CXCR4 (AMD3100) were evaluated in vitro. A preclinical perineural invasion model was developed using BALB/c nude mouse. The effect of AMD3100 was evaluated in vivo. Results. CXCR4 was highly expressed in aggressive strains of ACC in vitro, in the tumor in the animal model, and in the tumor of human tissue. SDF-1 expression was also demonstrated in the nerve of murine and human tissue. Gene knockdown by siRNA and inhibition by a CXCR4 specific inhibitor AMD3100 effectively abrogated invasion but not proliferation of ACC in vitro. The rate of perineural invasion was significantly decreased with AMD3100 treatment in the animal model (71.4% vs 18.8%, P=.009). Conclusions. CXCR4 is highly expressed in ACC and is associated with perineural invasion. AMD3100, which can effectively diminish perineural invasion of ACC in vitro and in vivo, may have an adjuvant role in the management of ACC. Citation Format: Woo-Jin Jeong, Ik Joon Choi, Min-Woo Park, Soo-Youn An, Eun-Hui Jeon, Jin Ho Paik, Myung-Whun Sung, Soon-Hyun Ahn. CXCR4 antagonist inhibits perineural invasion of adenoid cystic carcinoma in preclinical murine model. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr C20.