轴突导向分子EphA2/ephrinA1介导腺样囊性癌嗜神经侵袭的分子机制

项目名称： 轴突导向分子EphA2/ephrinA1介导腺样囊性癌嗜神经侵袭的分子机制

项目编号： No.81202143

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学2

项目作者： 邵喆

作者单位： 武汉大学

项目金额： 23万元

中文摘要： 嗜神经侵袭是腺样囊性癌(ACC)重要的生物学行为特征之一，其机制目前仍不清楚。轴突导向分子Eph/ephrin在发育过程中可以调节神经及血管系统的形成，在成体则参与调节肿瘤血管生成，那么Eph/ephrin在成体是否也参与了肿瘤与神经的相互作用？我们前期研究发现EphA2/ephrinA1在ACC组织中的表达与ACC嗜神经侵袭相关。综合已有的研究结果，我们推测EphA2/ephrinA1信号可能参与调节ACC嗜神经侵袭过程。本课题拟探讨以下内容：⑴ACC与神经相互作用过程中的细胞行为及分子表型的变化；⑵通过体外体内模型检测EphA2/ephrinA1在ACC嗜神经侵袭过程中的作用；⑶EphA2/ephrinA1对ACC嗜神经侵袭过程中细胞迁移、存活能力的分子调控。有望揭示EphA2/ephrinA1调节ACC嗜神经侵袭的作用机制，为深入理解肿瘤嗜神经侵袭的发生机制及肿瘤的防治提供线索。

中文关键词： 腺样囊性癌；嗜神经侵袭；肿瘤转移；EphA2；ephrinA1

英文摘要： Perineural invasion(PNI) is emerging as an important pathologic feature of adenoid cystic carcinoma(ACC). It can be a source of diffuse invasion and distant metastasis for ACC. Despite increasing recognition of this metastatic process, there has been little progress in the understanding of molecular mechanisms behind PNI. Axon guidance molecules Eph/ephrin could regulate the formation of nervous and vascular system in embryogenesis and tumor angiogenesis in adults. However, relative research on Eph/ephrin mediating interaction between tumor and nerve has not been found. In our previous study, we found a high expression of EphA2/ephrinA1 in ACC tissues and the nerve tissues invaded by ACC. The expression of EphA2/ephrinA1 was significantly correlated to perineural invasion of ACC. We propose that EphA2/ephrinA1 might be involved in the process of PNI in ACC and mediate the PNI through a series of signaling cascade. We plan to design the in vitro and in vivo models through which to investigate the mechanisms of PNI mediated by EphA2/ephrinA1. This research includes three parts. The first one is to investigate the behavior and phenotype change of ACC cells during the interaction between ACC cell and nerve tissue. The second one is to detect the function of EphA2/ephrinA1 during the process of PNI in ACC. The third

英文关键词： Adenoid Cystic Carcinoma；Perineural Invasion；Metastasis；EphA2；ephrinA1