Tumor microenvironment and Oral Squamous Cell Carcinoma: A crosstalk between the inflammatory state and tumor cell migration
Tumor microenvironment and Oral Squamous Cell Carcinoma: A crosstalk between the inflammatory state and tumor cell migration
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DOI：
10.1016/j.oraloncology.2020.105038
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发表时间：
2021-01-01
期刊：
影响因子：
4.8
通讯作者：
Lamers, Marcelo
中科院分区：
文献类型：
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作者：
Alves, Alessandro;Diel, Leonardo;Lamers, Marcelo
目的：为分析口腔鳞癌（oral squamous cell carcinoma，OSCC）肿瘤组织中的炎性环境及巨噬细胞相关细胞因子对肿瘤细胞迁移的影响，采用蛋白质组学和流式细胞术分析人口腔鳞癌组织中炎性蛋白表达谱和巨噬细胞数量（M2/M1）。为了评估炎症对OSCC行为的影响，我们通过蛋白质印迹（细胞信号传导）和延时（细胞迁移）分析了极化的巨噬细胞和细胞因子（IL-6，IL-1 β和TNF-α）对OSCC细胞系（SCC 25和Cal 27）反应性的作用。此外，使用STAT 3抑制剂（Stattic（R））和用于RhoGT 3 Rac 1活性的下拉测定来解决IL-6-STAT 3轴与细胞迁移信号传导的串扰。M2条件培养基增加了高度侵袭性OSCC细胞（SCC 25）的迁移速度和方向性。OSCC细胞系对细胞因子刺激（IL-6、IL-1 β和TNF-α）有反应，但只有IL-6增加OSCC细胞的迁移特性。这种作用依赖于STAT 3磷酸化水平，干扰Rac 1激活levels.Conclusion：我们的研究结果表明，炎症环境可能有利于巨噬细胞相关的细胞因子对肿瘤迁移的直接影响，OSCC的侵袭和转移。
Objectives: To analyze the inflammatory millieu in oral squamous cell carcinoma (OSCC) tumors and the influence of macrophages related-cytokines on the tumor cell migration.Materials and methods: Inflammatory protein profile and macrophage population (M2/M1 ratio) of human OSCC fragments were analyzed by proteomic analysis and flow cytometry assay respectively. To evaluate the effects of inflammation on OSCC behavior, we analyzed the role of polarized macrophages and cytokines (IL-6, IL-1 beta and TNF-alpha) on OSCC cell lines (SCC25 and Cal27) responsiveness by western blotting (cell signaling) and time-lapse (cell migration). Also, it was addressed the crosstalk of IL-6-STAT3 axis with cell migration signaling using a STAT3 inhibitor (Stattic (R)) and a pull down assay for the RhoGTPase Rac1 activity.Results: It was observed a similar to 2 fold predominance of M2 over M1 macrophages and a pro-inflammatory state in OSCC fragments. The M2 conditioned media increased migration speed and directionality of highly invasive OSCC cells (SCC25). OSCC cell lines were responsive to cytokine stimuli (IL6, IL-1 beta and TNF-alpha), but only IL-6 increased migration properties of OSCC cells. This effect was dependent on STAT3-phosphorylation levels, which interfered with Rac1 activation levels.Conclusion: Our results suggest that the inflammatory milieu might favor invasion and metastasis of OSCC by the direct effect of macrophage-related cytokines on tumor migration.