瘤相关的巨细胞由瘤衍生乳酸的功能极化
Oscar R Colegio1, Ngoc-Quynh Chu2, Alison L Szabo2
11] Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06519-1612, USA [2] Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut 06520-8059, USA [3] Yale-New Haven Transplantation Center, Yale University School of Medicine, New Haven, Connecticut 06519-1369, USA [4] Yale Cancer Center, Yale University School of Medicine, New Haven, Connecticut 06520-8028, USA.
Nature
|July 22, 2014
概括
来自瘤细胞的乳酸向与瘤相关的巨细胞发出信号,促进M2类的两极分化和阿基因酶1的表达,从而驱动瘤生长. 这突显了瘤和巨细胞之间的关键通讯途径.
科学领域:
- 免疫学 免疫学 免疫学
- 癌症生物学 癌症生物学
- 细胞信号传输 细胞信号传输
背景情况:
- 巨细胞对于组织平衡和监测辅酶细胞功能至关重要.
- 瘤模仿异常器官,与瘤相关的巨细胞 (TAMs) 支持瘤生长.
- 瘤和TAM之间的通信信号尚未得到充分理解.
研究的目的:
- 阐明瘤细胞和TAMs之间的信号机制.
- 确定乳酸在瘤-巨细胞通信中的作用.
- 调查这种沟通对瘤进展的影响.
主要方法:
- 对瘤细胞乳酸生成的分析.
- 对TAM两极分化和基因表达的评估.
- 调查缺氧诱导因素1α (HIF1α) 的参与.
- 在TAMs中对阿根酶1表达的评估.
主要成果:
- 由瘤细胞产生的乳酸诱导血管内皮生长因子 (VEGF) 表达和TAMs中的M2样极化.
- 这种效应是由低氧诱导因子1α (HIF1α) 介导的.
- 乳酸诱导的阿基因酶1通过TAMs的表达对瘤生长至关重要.
结论:
- 乳酸作为瘤微环境中的信号分子.
- 确定了一种新的瘤-巨细胞通讯途径,涉及乳酸,HIF1α和酶1.
- 这条为平衡而进化的通路被瘤劫持,以促进生长.
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