Abstract
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.
Highlights
Nasopharyngeal carcinoma (NPC) is the most common otorhinolaryngological tumor type originated from the epithelial cells [1, 2]
We found a large number of brown-yellow staining signals for S100A8 proteins in the intercellular space and tumor cell cytoplasm of these NPC tissues including phases II, III, and IV, while there was only a few brown-yellow staining in chronic pharyngitis (CP) tissues (Figures 1(a) and 1(b))
A large number of brownyellow staining signals for S100A9 proteins were detected in the intercellular space and tumor cell cytoplasm of these NPC tissues including phases II, III and IV, while only a few brown-yellow staining for S100A9 was observed in CP tissues (Figures 1(c) and 1(d)). e results indicated that abundant S100A8 and S100A9 proteins were expressed in NPC tissues including II, III and IV clinical stages, mainly distributed in the columnar epithelial interstitium and in the cytoplasm of NPC cells
Summary
Nasopharyngeal carcinoma (NPC) is the most common otorhinolaryngological tumor type originated from the epithelial cells [1, 2]. Nonkeratinized low differentiation NPC with high degree of malignancy is the main pathological type in clinical [7]. As high as 60–70% of the newly diagnosed NPC patients have already developed local advanced lesions [8, 9]. Along with the development of modern radiotherapy and chemotherapy, the initial treatment response rate currently reaches 90.9% for these NPC patients with advanced stages (III and IV stages) [10], and the five-year survival rate is 72.3–86% [11,12,13]. NPC often has a high incidence of recurrence and distant metastasis, especially for those patients with advanced stages. E recurrence and distant metastasis are causes of treatment failure for NPC patients. To better promote NPC prognosis and provide a rationale for novel therapies, it was absolutely essential to discover more promising biomarkers of NPC and unravel their underlying molecular mechanisms
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