Class A1 scavenger receptor modulates glioma progression by regulating M2-like tumor-associated macrophage polarization.
Class A1 scavenger receptor modulates glioma progression by regulating M2-like tumor-associated macrophage polarization.
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A1 类清道夫受体通过调节 M2 样肿瘤相关巨噬细胞极化来调节神经胶质瘤进展
DOI：
10.18632/oncotarget.10318
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发表时间：
2016-08-02
期刊：
影响因子：
--
通讯作者：
Chen Q
中科院分区：
文献类型：
--
作者：
Zhang H;Zhang W;Sun X;Dang R;Zhou R;Bai H;Ben J;Zhu X;Zhang Y;Yang Q;Xu Y;Chen Q
巨噬细胞通过塑造肿瘤微环境促进胶质瘤的发展和进展。A1类清道夫受体（SR-A1）是一种主要在巨噬细胞中表达的模式识别受体，在许多人类实体瘤中上调。我们发现SR-A1在136例人脑胶质瘤中的表达与肿瘤分级呈正相关（P<0.01），而与预后和肿瘤复发无关。表达SR-A1的巨噬细胞主要来源于被肿瘤组织吸引的循环单核细胞，其数量几乎是胶质瘤组织中常驻小胶质细胞的两倍（P<0.001）。使用SR-A1缺陷的鼠原位胶质瘤模型在体内评估SR-A1对胶质瘤增殖和侵袭的影响。SR-A1缺失通过激活STAT 3和STAT 6促进小鼠中M2样肿瘤相关巨噬细胞（TAM）极化，从而导致稳定的原位胶质瘤增殖和血管生成。最后，我们发现，热休克蛋白70可能是一种内源性配体，激活SR-A1依赖的抗肿瘤通路在胶质瘤，虽然它的表达并没有出现诊断目的的信息。我们的研究结果表明TAM，SR-A1表达和胶质瘤生长之间的关系，并提供了新的见解TAM在胶质瘤中的致病作用。
Macrophages enhance glioma development and progression by shaping the tumor microenvironment. Class A1 scavenger receptor (SR-A1), a pattern recognition receptor primarily expressed in macrophages, is up-regulated in many human solid tumors. We found that SR-A1 expression in 136 human gliomas was positively correlated with tumor grade (P<0.01), but not prognosis or tumor recurrence. SR-A1-expressing macrophages originated primarily from circulating monocytes attracted to tumor tissue, and were almost twice as numerous as resident microglia in glioma tissues (P<0.001). The effects of SR-A1 on glioma proliferation and invasion were assessed in vivo using an SR-A1-deficient murine orthotopic glioma model. SR-A1 deletion promoted M2-like tumor-associated macrophage (TAM) polarization in mice by activating STAT3 and STAT6, which resulted in robust orthotopic glioma proliferation and angiogenesis. Finally, we found that HSP70 might be an endogenous ligand that activates SR-A1-dependent anti-tumorigenic pathways in gliomas, although its expression does not appear informative for diagnostic purposes. Our findings demonstrate a relationship between TAMs, SR-A1 expression and glioma growth and provide new insights into the pathogenic role of TAMs in glioma.