头颈癌因其恶性进展严重危害人类健康，且机制未完全阐明。新近发现外泌体可调控肿瘤细胞间及其与微环境之间通讯而影响其恶性生物学行为，促进肿瘤恶性进展，但外泌体分泌调控机理不清。钙作为重要的第二信使，可能参与其过程。本课题组前期发现头颈癌组织高表达钙通道TRPP2且与其恶性进展正相关，TRPP2高表达的头颈癌细胞外泌体对血管内皮细胞有更强的促增殖作用，敲低TRPP2可显著降低胞内Ca2+水平、外泌体数量并可能改变蛋白成份，且头颈癌细胞中TRPP2与其囊泡转运系统成份Sec6/10、外泌体标志分子CD63及肌动蛋白共定位并相互作用。据此我们推测钙通道TRPP2可能参与头颈癌细胞外泌体分泌调控，且可能通过影响血管新生等参与头颈癌的恶性进展。本项目拟利用细胞、动物模型和临床标本，明确TRPP2是否通过调节头颈癌细胞外泌体分泌量和成份而促进其恶性生物学行为，并阐明其具体机制，为头颈癌的治疗提供新思路。

Head and neck cancer has become a serious health problem in human due to its malignant progression, but the underlyig mechanisms remain elusive. Exosomes can regulate the communication within tumor cells, and between tumor cells and tumor microenvironment, which promote malignant progression of tumor. However, the regulatory mechanism of exosome secretion is not clear. Calcium, as an important second messenger, may have important role in the process of exosome secretion. Our previous studies revealed that the high expression level of calcium channel TRPP2 was positively correlated with tumor malignant progression in head and neck cancer. A strong proliferation-promoting effect on vascular endothelial cells was observed when cultured by culture medium with exosomes from high expressing TRPP2 head and neck cancer cells. TRPP2 knockdown significantly decreased intracellular Ca2+ concentration and exosome numbers, and changed the protein composition. Of note, TRPP2 interacted with the vesicular transport component Sec6 and Sec 10, the exosome marker CD63 in head and neck cancer cells. Therefore, we hypothesized that calcium channel TRPP2 promotes the antiogenesis and malignant progression of head and neck cancer by promoting the formation and secretion of exosome. In this project, we plan to investigate the mechanism of TRPP2 affecting the formation and secretion of exosome both in vitro, and in vivo levels. The association between TRPP2 levels, exosome secretion, and malignant progression will be observed in the head and neck cancer patients. This project might provide a new idea for the prevention and treatment of head and neck cancer.