Tumor-associated macrophages in breast cancer: distinct subsets, distinct functions

被引:241
作者
Laoui, Damya
Movahedi, Kiavash
Van Overmeire, Eva
Van den Bossche, Jan
Schouppe, Elio
Mommer, Camille
Nikolaou, Alexandros
Morias, Yannick
De Baetselier, Patrick
Van Ginderachter, Jo A.
机构
[1] Vrije Univ Brussel, Dept Mol & Cell Interact, Lab Cellular & Mol Immunol, Brussels, Belgium
[2] Vrije Univ Brussel, Dept Mol & Cell Interact, Lab Cellular & Mol Immunol, Brussels, Belgium
关键词
tumor-associated macrophage; mammary carcinoma; breast cancer; tumor microenvironment; M2; HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; MAMMARY-GLAND DEVELOPMENT; ENDOTHELIAL GROWTH-FACTOR; GENE-EXPRESSION ANALYSIS; MYELOID CELLS; ALTERNATIVE ACTIVATION; IN-VIVO; KAPPA-B; ANGIOGENESIS; PROGRESSION;
D O I
10.1387/ijdb.113371dl
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Macrophages display remarkable plasticity, allowing these cells to adapt to changing microenvironments and perform functions as diverse as tissue development and homeostasis, inflammation, pathogen clearance and wound healing. Macrophage activation can be triggered by Th1 cytokines and pathogen-associated or endogenous danger signals, leading to the formation of classically activated or M1 macrophages. On the other hand, anti-inflammatory mediators, including IL-4, IL-10,TGF-beta and M-CSF, induce diverse anti-inflammatory types of macrophages, known under the generic term M2. In human breast carcinomas, tumor-associated macrophage (TAM) density correlates with poor prognosis. In mouse models of breast cancer, eliminating macrophages from the tumor site, either via genetic or therapeutic means, results in retarded tumor progression. Over the years, multiple signals from the mammary tumor microenvironment have been reported to influence the TAM phenotype and TAM have been propagated as anti-inflammatory M2-like cells. Recent developments point to the existence of at least two distinct TAM subpopulations in mammary tumors, based on a differential expression of markers such as CD206 or MHC II and different in vivo behaviour: perivascular, migratory TAM which are less M2-like, and sessile TAM found at tumor-stroma borders and/or hypoxic regions that resemble more M2-like or "trophic" macrophages. Hence, a further refinement of the molecular and functional heterogeneity of TAM is an avenue for further research, with a potential impact on the usefulness of these cells as therapeutic targets.
引用
收藏
页码:861 / 867
页数:7
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