TGF-β/MMP9/RAGE轴诱导中性粒细胞的sRAGE分泌,并促进口腔癌发生
Xiaolin Chen1, Ningyuan Wang1, Chenyang Jing1
1Faculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, China.
Biochemistry and biophysics reports
|March 11, 2024
概括
转化生长因子β (TGF-β) 驱使中性粒细胞促进口腔癌. 这项研究揭示了TGF-β对先进的糖化终产品 (sRAGE) 的可溶性受体进行高调节,这是口腔状细胞癌进展的关键因素.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 分子生物学分子生物学
背景情况:
- 转化生长因子β (TGF-β) 影响瘤微环境中的中性粒细胞表型.
- 通过TGF-β促进前瘤中性粒细胞的确切机制尚未完全理解.
研究的目的:
- 调查TGF-β在N2中性粒细胞两极化中的作用.
- 为了确定TGF-β诱导的N2中性粒细胞对口腔白血病/口腔状细胞癌 (OL/OSCC) 细胞的影响.
- 为了阐明参与这种相互作用的分子通路.
主要方法:
- 对N2中性粒细胞培养超物的细胞因子阵列分析.
- 对中性粒细胞中高级糖化终产品 (RAGE) 和矩阵金属蛋白酶9 (MMP9) 表达的受体的评估.
- 在体内研究使用4NQO诱导的口腔癌小鼠模型.
- 对癌症基因组图谱 (TCGA) 数据库对头部和部状细胞癌 (HNSCC) 数据的分析.
主要成果:
- TGF-β刺激导致N2中性粒细胞的两极分化,并增加了OL/OSCC细胞的增殖.
- 在TGF-β刺激的N2中性粒细胞中观察到可溶性RAGE (sRAGE) 的升高.
- TGF-β诱导中性粒细胞中的RAGE和MMP9表达;MMP9分裂RAGE,促进其分泌和癌细胞增殖.
- 在小鼠中,RAGE 中和抑制了口腔癌的进展.
- 在HNSCC中,RAGE和MMP9的表达很高,RAGE与中性粒细胞透呈正相关.
结论:
- TGF-β促进N2中性粒细胞的两极分化,导致sRAGE的分泌量增加,从而推动OSCC细胞的增殖.
- TGF-β诱导的sRAGE通路代表了OL/OSCC的潜在治疗标.
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