TGF-β1可激活中性粒细胞信号传递和基因表达,但不能激活迁移
Lauren E Hein1,2, Shuvasree SenGupta3, Gaurie Gunasekaran3,4
1Cancer Biology Graduate Program, University of Michigan Medical School, Ann Arbor, MI, United States of America.
PloS one
|September 8, 2023
概括
转化生长因子-β (TGF-β) 激活中性粒细胞的关键信号通路,但不会直接诱导它们的迁移. 瘤条件介质触发中性粒细胞释放白血素B4 (LTB4),影响瘤微环境.
科学领域:
- 免疫学 免疫学 免疫学
- 癌症生物学 癌症生物学
- 细胞信号传递 细胞信号传递
背景情况:
- 与瘤相关的中性粒细胞 (TAN) 与癌症的不良结果有关.
- 在瘤微环境中转化生长因子-β (TGF-β) 可能促进前瘤中性粒细胞表型.
- 对于TGF-β对中性粒细胞信号传递和迁移的确切影响尚不完全理解.
研究的目的:
- 为了研究TGF-β在人类初级中性粒细胞和HL-60细胞中的信号传递.
- 为了确定TGF-β是否直接诱导中性粒细胞迁移.
- 阐明TGF-β在瘤微环境中的中性粒细胞激活和基因表达中的作用.
主要方法:
- 使用过井和低藻迁移试验来评估中性粒细胞化学反应.
- 研究了TGF-β信号通路,包括SMAD3和ERK1/2激活.
- 使用RNA测序分析基因表达的变化,并测量了白血素B4 (LTB4) 分泌.
主要成果:
- TGF-β1并没有直接诱导中性粒细胞迁移.
- 在中性粒细胞中,TGF-β1激活了正规 (SMAD3) 和非正规 (ERK1/2) 信号通路.
- 瘤条件介质 (TCM) 诱导了中性粒细胞的LTB4分泌,但单独的TGF-β1没有.
- TGF-β1和TCM改变了瘤基因的表达,比如 Kostatin M (OSM) 和血管内皮生长因子A (VEGFA).
结论:
- TGF-β1调节中性粒细胞信号传递和基因表达,但不直接驱动迁移.
- 中性粒细胞的TCM诱导的LTB4释放表明了瘤中放大中性粒细胞招募的机制.
- 这些发现为TGF-β在塑造瘤微环境中的中性粒细胞行为的复杂作用提供了关键的见解.
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