Functional polarization of tumour-associated macrophages by tumour-derived lactic acid.
Functional polarization of tumour-associated macrophages by tumour-derived lactic acid.
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DOI：
10.1038/nature13490
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发表时间：
2014-09-25
期刊：
影响因子：
64.8
通讯作者：
Medzhitov, Ruslan
中科院分区：
文献类型：
--
作者：
Colegio, Oscar R.;Ngoc-Quynh Chu;Szabo, Alison L.;Chu, Thach;Rhebergen, Anne Marie;Jairam, Vikram;Cyrus, Nika;Brokowski, Carolyn E.;Eisenbarth, Stephanie C.;Phillips, Gillian M.;Cline, Gary W.;Phillips, Andrew J.;Medzhitov, Ruslan
巨噬细胞在维持组织稳态中起着重要作用。为了实现这一功能，巨噬细胞必须有能力监测其“客户细胞”的功能状态，即巨噬细胞所在的各种组织中的实质细胞。肿瘤表现出器官异常发育的许多特征，包括组织结构和细胞组成。与正常组织和器官中的巨噬细胞类似，肿瘤中的巨噬细胞（肿瘤相关巨噬细胞）执行一些关键的稳态功能，使肿瘤维持和生长，，。然而，参与肿瘤和巨噬细胞之间交流的信号尚未明确。本研究表明，由肿瘤细胞产生的乳酸作为有氧或厌氧糖酵解的副产物，通过诱导血管内皮生长因子的表达和肿瘤相关巨噬细胞的m2样极化，在信号传导中具有关键功能。此外，我们证明乳酸的这种作用是由缺氧诱导因子1α (HIF1α)介导的。最后，我们发现巨噬细胞中乳酸诱导的精氨酸酶1的表达在肿瘤生长中具有重要作用。总的来说，这些发现确定了巨噬细胞与其客户细胞（包括肿瘤细胞）之间的通信机制。这种交流很可能是为了促进正常组织的内稳态而进化的，但也可以参与肿瘤以促进其生长。
Macrophages have an important role in the maintenance of tissue homeostasis. To perform this function, macrophages must have the capacity to monitor the functional states of their ‘client cells’: namely, the parenchymal cells in the various tissues in which macrophages reside. Tumours exhibit many features of abnormally developed organs, including tissue architecture and cellular composition. Similarly to macrophages in normal tissues and organs, macrophages in tumours (tumour-associated macrophages) perform some key homeostatic functions that allow tumour maintenance and growth,,. However, the signals involved in communication between tumours and macrophages are poorly defined. Here we show that lactic acid produced by tumour cells, as a by-product of aerobic or anaerobic glycolysis, has a critical function in signalling, through inducing the expression of vascular endothelial growth factor and the M2-like polarization of tumour-associated macrophages. Furthermore, we demonstrate that this effect of lactic acid is mediated by hypoxia-inducible factor 1α (HIF1α). Finally, we show that the lactate-induced expression of arginase 1 by macrophages has an important role in tumour growth. Collectively, these findings identify a mechanism of communication between macrophages and their client cells, including tumour cells. This communication most probably evolved to promote homeostasis in normal tissues but can also be engaged in tumours to promote their growth.
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DOI：
10.1038/nri2528
发表时间：
2009-04
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1038/nri3073
发表时间：
2011-10-14
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
64.8
作者：
SHWEIKI, D;ITIN, A;KESHET, E
通讯作者：
KESHET, E
影响因子：
64.5
作者：
Qian BZ;Pollard JW
通讯作者：
Pollard JW
影响因子：
4.2
作者：
Wynn TA;Barron L
通讯作者：
Barron L