Rojas Armando, Araya Paulina, Romero Jacqueline, Delgado-López Fernando, Gonzalez Ileana, Añazco Carolina, Perez-Castro Ramon
Biomedical Research Labs., Medicine Faculty, Catholic University of Maule, 3605 San Miguel Ave, Talca, Chile.
Cancer Microenviron. 2018 Dec;11(2-3):97-105. doi: 10.1007/s12307-018-0214-4. Epub 2018 Aug 8.
Tumors are complex tissues composed of variable amounts of both non-cellular components (matrix proteins) and a multitude of stromal cell types, which are under an active cross-talk with tumor cells. Tumor-associated macrophages (TAMs) are the major leukocyte population among the tumor-infiltrating immune cells. Once they are infiltrated into tumor stroma they undergo a polarized activation, where the M1 and M2 phenotypes represent the two extreme of the polarization heterogeneity spectrum. It is known that TAMs acquire a specific phenotype (M2), oriented toward tumor growth, angiogenesis and immune-suppression. A growing body of evidences supports the presence of tuning mechanisms in order to skew or restraint the inflammatory response of TAMs and thus forces them to function as active tumor-promoting immune cells. The receptor of advanced glycation end-products (RAGE) is a member of the immunoglobulin protein family of cell surface molecules, being activated by several danger signals and thus signaling to promote the production of many pro-inflammatory molecules. Interestingly, this receptor is paradoxically expressed in both M1 and M2 macrophages phenotypes. This review addresses how RAGE signaling has been drifted away in M2 macrophages, and thus taking advantage of the abundance of RAGE ligands at tumor microenvironment, particularly HMGB1, to reinforce the supportive M2 macrophages strategy to support tumor growth.
肿瘤是复杂的组织，由数量不等的非细胞成分（基质蛋白）和多种基质细胞类型组成，这些细胞与肿瘤细胞之间存在活跃的相互作用。肿瘤相关巨噬细胞（TAM）是肿瘤浸润免疫细胞中的主要白细胞群体。一旦它们浸润到肿瘤基质中，就会经历极化激活，其中M1和M2表型代表极化异质性谱的两个极端。已知TAM会获得一种特定的表型（M2），倾向于肿瘤生长、血管生成和免疫抑制。越来越多的证据支持存在调节机制，以倾斜或抑制TAM的炎症反应，从而迫使它们发挥积极的促进肿瘤的免疫细胞功能。晚期糖基化终产物受体（RAGE）是细胞表面分子免疫球蛋白蛋白家族的成员，被多种危险信号激活，从而发出信号促进许多促炎分子的产生。有趣的是，这种受体在M1和M2巨噬细胞表型中都有反常表达。这篇综述探讨了RAGE信号在M2巨噬细胞中是如何偏离的，从而利用肿瘤微环境中丰富的RAGE配体，特别是高迁移率族蛋白B1（HMGB1），来加强支持肿瘤生长的M2巨噬细胞策略。
