我们前期发现分泌性蛋白PLUNC在鼻咽癌中表达下调且与患者不良预后相关，鼻咽癌细胞中重表达PLUNC能抑制鼻咽癌细胞侵袭转移；利用免疫共沉淀-质谱分析（immunoprecipitation-mass spectrometry，IP-MS）及免疫共沉淀技术我们发现PLUNC与细胞外基质蛋白Vitronectin（VTN）存在交互作用，本项目提出“PLUNC可能通过与VTN相互作用并下调VTN的表达、调控整合素下游STAT3/Akt/Erk1/2信号通路抑制鼻咽癌侵袭转移；以及通过VTN作用微环境中的肿瘤相关成纤维细胞（tumor associated fibroblasts, TAFs），尽可能降低TAFs分泌相关细胞因子和基质金属蛋白酶，减少细胞外基质的降解，从而抑制肿瘤微环境在鼻咽癌细胞侵袭转移中的作用”这一假说。本项目将初步明晰PLUNC这一固有免疫分子抑制鼻咽癌侵袭转移的分子机制。

In our previous projects, we have found that the secreted protein PLUNC is down-regulated in nasopharyngeal carcinoma (NPC) and is associated with poor prognosis of NPC patients. Re-expression PLUNC in NPC cells could inhibit NPC cell invasion and metastasis. Through immunoprecipitation-mass spectrometry (IP-MS) and Co-IP, we found that there is an interaction between PLUNC and extracellular matrix protein Vitronectin (VTN). We hypothesize that PLUNC interacts with VTN and down-regulates the expression of VTN, then inhibits NPC cell invasion and metastasis through regulating integrin downstream STAT3/Akt/Erk1/2 signaling pathway. In addition, PLUNC interacts with VTN and affects the tumor microenvironment (especially the tumor associated fibroblasts, TAFs) and reduces the secretion of cytokines and matrix metalloproteinase (MMP) as far as possible, then reduces the degradation of extracellular matrix (ECM) and inhibits invasion and metastasis of NPC by the tumor microenvironment. In this study, we aim to elucidate in detail the role and mechanism of innate immune protein PLUNC in inhibiting invasion and metastasis of NPC.