He Yungang, Deng Pingmeng, Yan Ying, Zhu Luying, Chen Hongying, Li Ting, Li Yong, Li Jie
College of Stomatology, Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China.
College of Stomatology, Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China.
J Proteomics. 2022 Feb 20;253:104454. doi: 10.1016/j.jprot.2021.104454. Epub 2021 Dec 16.
Oral squamous cell carcinoma (OSCC) is a common pernicious tumor in the head and neck regions. However, the function of tumor extracellular matrix (ECM) has not been elucidated. A tissue engineering method was applied for remodeling ECM through decellularization. The cellular components were removed, and the biological composition was mostly preserved. Proteomics was performed to analyze the characterization between normal and tumor ECM. According to LC-MS/MS results, 26 proteins just showed in tumor ECM, and 14 proteins only showed in late-stage tumor ECM. KEGG pathway analysis showed that most variant proteins were linked to metabolic regulation and tumor immunity (such as SCC-Ag1, LOX). To affirm the influence of tumor ECM on the progression of OSCC, tumor cells and macrophages were co-cultured with ECM scaffold. Marked differences in proliferation, apoptosis, and migration of OSCC cells were observed between tumor and normal ECM. Tumor ECM polarized macrophages towards an anti-inflammatory phenotype (higher IL-10 and CD68, and relatively lower CD86 and IL1-β). Collectively, these findings suggest that tumor ECM served as a permissive role in OSCC progression. SIGNIFICANCE: The variation between OSCC ECM and normal ECM confirm tumor ECM plays a significant role in OSCC deterioration, which is conducive to exploring the occurrence and progression mechanisms of OSCC, and further improving the curative effect of this disease.
口腔鳞状细胞癌(OSCC)是头颈部常见的恶性肿瘤。然而,肿瘤细胞外基质(ECM)的功能尚未阐明。采用组织工程方法通过去细胞化对ECM进行重塑。去除细胞成分,大部分生物成分得以保留。进行蛋白质组学分析以研究正常和肿瘤ECM之间的特征。根据液相色谱-串联质谱(LC-MS/MS)结果,26种蛋白质仅在肿瘤ECM中出现,14种蛋白质仅在晚期肿瘤ECM中出现。京都基因与基因组百科全书(KEGG)通路分析表明,大多数变异蛋白与代谢调节和肿瘤免疫相关(如鳞状细胞癌抗原1、赖氨酰氧化酶)。为了确定肿瘤ECM对OSCC进展的影响,将肿瘤细胞和巨噬细胞与ECM支架共培养。在肿瘤ECM和正常ECM之间观察到OSCC细胞在增殖、凋亡和迁移方面存在显著差异。肿瘤ECM使巨噬细胞极化为抗炎表型(白细胞介素-10和CD68较高,而CD86和白细胞介素-1β相对较低)。总体而言,这些发现表明肿瘤ECM在OSCC进展中起促进作用。意义:OSCC的ECM与正常ECM之间的差异证实肿瘤ECM在OSCC恶化中起重要作用,这有助于探索OSCC的发生和进展机制,并进一步提高该病的治疗效果。