Monocyte-derived macrophages promote breast cancer bone metastasis outgrowth.
Monocyte-derived macrophages promote breast cancer bone metastasis outgrowth.
复制标题
单核细胞源性巨噬细胞促进乳腺癌骨转移生长
DOI：
10.1084/jem.20191820
复制
发表时间：
2020-11-02
期刊：
影响因子：
--
通讯作者：
Qian BZ
中科院分区：
文献类型：
--
作者：
Ma RY;Zhang H;Li XF;Zhang CB;Selli C;Tagliavini G;Lam AD;Prost S;Sims AH;Hu HY;Ying T;Wang Z;Ye Z;Pollard JW;Qian BZ
本研究在小鼠模型和患者样本中鉴定了一种新的CD 204 + IL 4 R+骨转移相关巨噬细胞（BoMAMs）群体。这些BoMAMs来源于CCR 2募集的单核细胞，而不是CD 169+驻留的巨噬细胞，在体内显著促进乳腺癌的转移性生长。骨转移是乳腺癌死亡的主要原因。缺乏有效的治疗表明，疾病的机制在很大程度上仍然是未知的。巨噬细胞作为肿瘤微环境的关键成分，促进肿瘤的进展和转移。在这项研究中，我们发现巨噬细胞丰富的人类和小鼠乳腺癌骨转移。巨噬细胞消融显著抑制骨转移生长。谱系追踪实验表明，这些巨噬细胞主要来源于Ly 6C + CCR 2+炎性单核细胞。消融趋化因子受体CCR 2，显著抑制骨转移生长并延长生存期。免疫表型鉴定表明骨转移相关巨噬细胞表达高水平的CD 204和IL 4 R。此外，单核细胞/巨噬细胞限制性IL 4 R消融显著抑制骨转移生长，IL 4 R无效突变单核细胞未能促进骨转移生长。总之，这项研究确定了单核细胞衍生的巨噬细胞的一个子集，促进乳腺癌骨转移的IL 4 R依赖性的方式。这表明IL 4 R和巨噬细胞抑制可以对乳腺癌骨疾病具有潜在的治疗益处。
This study identifies a novel population of CD204+IL4R+ bone metastasis–associated macrophages (BoMAMs) in mouse models and patient samples. These BoMAMs, derived from CCR2-recruited monocytes but not from CD169+ resident macrophages, significantly promote metastatic outgrowth of breast cancer in vivo. Bone metastasis is the major cause of death in breast cancer. The lack of effective treatment suggests that disease mechanisms are still largely unknown. As a key component of the tumor microenvironment, macrophages promote tumor progression and metastasis. In this study, we found that macrophages are abundant in human and mouse breast cancer bone metastases. Macrophage ablation significantly inhibited bone metastasis growth. Lineage tracking experiments indicated that these macrophages largely derive from Ly6C+CCR2+ inflammatory monocytes. Ablation of the chemokine receptor, CCR2, significantly inhibited bone metastasis outgrowth and prolonged survival. Immunophenotyping identified that bone metastasis–associated macrophages express high levels of CD204 and IL4R. Furthermore, monocyte/macrophage-restricted IL4R ablation significantly inhibited bone metastasis growth, and IL4R null mutant monocytes failed to promote bone metastasis outgrowth. Together, this study identified a subset of monocyte-derived macrophages that promote breast cancer bone metastasis in an IL4R-dependent manner. This suggests that IL4R and macrophage inhibition can have potential therapeutic benefit against breast cancer bone disease.
登录
查看更多内容
LY6C+“炎症单核细胞”是在西尼罗河病毒脑炎中以致病方式募集的小胶质前体。
DOI：
10.1084/jem.20080421
发表时间：
2008-09-29
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Getts DR;Terry RL;Getts MT;Müller M;Rana S;Shrestha B;Radford J;Van Rooijen N;Campbell IL;King NJ
通讯作者：
King NJ
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
7.2
作者：
Gupta, Sahil;Jain, Arpit;Namgaladze, Dmitry
通讯作者：
Namgaladze, Dmitry
肿瘤相关巨噬细胞的细胞和分子起源。
DOI：
10.1126/science.1252510
发表时间：
2014-05-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Franklin RA;Liao W;Sarkar A;Kim MV;Bivona MR;Liu K;Pamer EG;Li MO
通讯作者：
Li MO
影响因子：
14
作者：
Batoon, Lena;Millard, Susan Marie;Pettit, Allison Robyn
通讯作者：
Pettit, Allison Robyn