EB 病毒 (EBV) 相关鼻咽癌 (NPC) 细胞具有高转移潜力。近年来的研究表明，肿瘤细胞与周围间质之间的相互作用在肿瘤侵袭和转移中发挥着重要作用。在这项研究中，我们展示了 SPARC（一种具有多种细胞功能的细胞外基质蛋白）在鼻咽癌周围正常邻近组织 (NAT) 中表达的预后价值。在 51 例鼻咽癌活检标本的免疫组织化学分析中，与 EBER 阴性鼻咽癌的 NAT 相比，EBER（EBV 编码的小 RNA）阳性鼻咽癌的 NAT 中 SPARC 表达水平显着升高。此外，NAT 中 SPARC 表达的增加与总生存期的恶化相关。对公开的NPC和NPC周围的NAT数据进行RNA-seq富集分析表明，NPC中SPARC的高表达与上皮间质转化促进相关，并且NAT中与干扰细胞增殖相关的基因表达谱存在动态变化，包括 SPARC 表达式。此外，EBV阳性NPC细胞通过外泌体诱导正常鼻咽细胞中SPARC的表达。癌症周围 NAT 细胞中 SPARC 的诱导减少了正常鼻咽结构中的细胞间粘附，并促进了癌细胞与正常上皮细胞之间的细胞竞争。这些结果表明，上皮细胞放松了自身与细胞外基质以及基质细胞的结合，通过激活细胞竞争促进肿瘤细胞侵入邻近基质。我们的研究结果揭示了一种新机制，EBV 通过上调 NPC 中的 SPARC 表达来创建促转移微环境。© 2023 UICC。

Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) cells have high metastatic potential. Recent research has revealed that the interaction of between tumor cells and the surrounding stroma plays an important role in tumor invasion and metastasis. In this study, we showed the prognostic value of expression of SPARC, an extracellular matrix protein with multiple cellular functions, in normal adjacent tissues (NAT) surrounding NPC. In the immunohistochemical analysis of 51 NPC biopsy specimens, SPARC expression levels were significantly elevated in the NAT of EBER (EBV-encoded small RNA)-positive NPC compared to that in the NAT of EBER-negative NPC. Moreover, increased SPARC expression in NAT was associated with a worsening of overall survival. The enrichment analysis of RNA-seq of publicly available NPC and NAT surrounding NPC data showed that high SPARC expression in NPC was associated with epithelial mesenchymal transition promotion, and there was a dynamic change in the gene expression profile associated with interference of cellular proliferation in NAT, including SPARC expression. Furthermore, EBV-positive NPC cells induce SPARC expression in normal nasopharyngeal cells via exosomes. Induction of SPARC in cancer-surrounding NAT cells reduced intercellular adhesion in normal nasopharyngeal structures and promoted cell competition between cancer cells and normal epithelial cells. These results suggest that epithelial cells loosen their own binding with the extracellular matrix as well as stromal cells, facilitating the invasion of tumor cells into the adjacent stroma by activating cell competition. Our findings reveal a new mechanism by which EBV creates a pro-metastatic microenvironment by upregulating SPARC expression in NPC.© 2023 UICC.