Nasopharyngeal carcinoma (NPC) is one type of malignancy associated with migration and invasion through a currently unclear mechanism. We previously discovered S100A8/A9 levels were roughly elevated in the plasma of NPC patients as the promising biomarkers. However, their expressions and underlying functions in NPC tissues are still unknown. In the present study, we analyzed 49 NPC tissues and 20 chronic pharyngitis (CP) tissues. Immunohistochemical staining was performed in different tissues and analyzed by the Mann–Whitney U test statistically. Transwell migration and invasion experiments were further performed to determine S100A8/A9 effects on NPC. Our results showed that S100A8/A9 in NPC tissues were significantly higher than those in CP tissues, closely associated with NPC clinical stages. Intriguingly, exogenous S100A8/A9 protein stimulation could dramatically enhance NPC migration and invasion abilities. In addition, p38 MAPK pathway blockade could diminish the migration and invasion of NPC cells stimulated by S100A8/A9 proteins. The downstream tumor invasion and migration associated proteins (e.g., MMP7) were also elevated in NPC tissues, consistent with S100A8/A9 overexpression. Taken together, our present findings suggest that the secreted soluble inflammatory factors S100A8/A9 might promote cancer migration and invasion via the p38 MAPK signaling pathway along with invasion/migration associated proteins overexpression in the tumor microenvironment of NPC. This may shed light on the mechanism understanding of NPC prognosis and provide more novel clues for NPC diagnosis and therapy.

中文翻译：

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S100A8/A9 分子复合物通过 p38 MAPK 通路促进鼻咽癌中的癌症迁移和侵袭


鼻咽癌（NPC）是一种与迁移和侵袭相关的恶性肿瘤，其机制目前尚不清楚。我们之前发现鼻咽癌患者血浆中的 S100A8/A9 水平大致升高，这是有希望的生物标志物。然而，它们在鼻咽癌组织中的表达和潜在功能仍不清楚。在本研究中，我们分析了 49 例鼻咽癌组织和 20 例慢性咽炎 (CP) 组织。在不同组织中进行免疫组织化学染色，并通过 Mann-Whitney U检验进行统计分析。进一步进行Transwell迁移和侵袭实验以确定S100A8/A9对NPC的影响。我们的结果显示，鼻咽癌组织中的S100A8/A9显着高于鼻咽癌组织中的S100A8/A9，且与鼻咽癌临床分期密切相关。有趣的是，外源S100A8/A9蛋白刺激可以显着增强NPC的迁移和侵袭能力。此外，p38 MAPK 通路阻断可以减少 S100A8/A9 蛋白刺激的鼻咽癌细胞的迁移和侵袭。下游肿瘤侵袭和迁移相关蛋白（例如 MMP7）在 NPC 组织中也升高，与 S100A8/A9 过表达一致。综上所述，我们目前的研究结果表明，分泌的可溶性炎症因子 S100A8/A9 可能通过 p38 MAPK 信号通路以及鼻咽癌肿瘤微环境中侵袭/迁移相关蛋白的过度表达促进癌症迁移和侵袭。这可能有助于阐明鼻咽癌预后的机制，并为鼻咽癌的诊断和治疗提供更多新的线索。