氧化应激通过Thbs1-介导的M1-类瘤相关的巨细胞两极化促进口腔癌发生
Wei Li1, Qingwen Zeng1, Bing Wang1
1Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China.
Redox biology
|September 10, 2024
概括
缺失ASCT2会导致氧化应激,并通过调节Thbs1和M1巨细胞两极分化来促进口腔癌. 恢复氧化还原平衡可能会防止口腔癌的进展.
科学领域:
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
- 癌症研究 癌症研究
背景情况:
- 氧化应激与口腔癌的侵袭和转移有关,但其在早期阶段的作用尚不清楚.
- 氨酸-氨酸-氨酸运输体2 (ASCT2) 调节谷氨酸的摄取,以合成谷氨,这对于解决氧化应激至关重要.
研究的目的:
- 研究ASCT2缺失诱导的氧化应激在口腔癌发生中的作用.
- 阐明ASCT2影响口腔癌进展和巨细胞两极分化的机制.
主要方法:
- 使用ASCT2淘汰赛转基因小鼠和4-Nitroquinoline-1-oxide (4-NQO) 诱导用于口腔致癌.
- 采用mRNA测序,免疫组织化学和多重免疫组织化学来分析基因表达和免疫细胞透.
- 研究了口腔角质细胞和巨细胞中的信号通路 (p38,Akt,SAPK/JNK) 和外体介导通信.
主要成果:
- 口腔表皮中的ASCT2缺失导致了氧化应激,并促进了4-NQO诱导的口腔癌发生.
- 观察到Thbs1的升调,与巨细胞透率的增加和M1-类瘤相关巨细胞 (TAMs) 的丰富相关.
- 针对ASCT2导致ROS积累,Thbs1上调和M1-样TAM偏振通过外体转移,促进口腔状细胞癌 (OSCC) 的进展.
结论:
- 由ASCT2缺失引起的氧化应激通过Thbs1-介导的M1 TAM两极化促进口腔癌发生.
- 准ASCT2和恢复氧化还原平衡是预防口腔癌进展的潜在策略.
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