2. Academic Validation
  3. Monocyte-derived macrophages promote breast cancer bone metastasis outgrowth

Monocyte-derived macrophages promote breast cancer bone metastasis outgrowth

  • J Exp Med. 2020 Nov 2;217(11):e20191820. doi: 10.1084/jem.20191820.
Ruo-Yu Ma 1,  Hui Zhang 2,  Xue-Feng Li 1,  Cheng-Bin Zhang 1,  Cigdem Selli 1,  Giulia Tagliavini 3,  Alyson D Lam 1,  Sandrine Prost 3,  Andrew H Sims 4,  Hai-Yan Hu 5,  Tianlei Ying 6,  Zhan Wang 7,  Zhaoming Ye 7,  Jeffrey W Pollard 1 2,  Bin-Zhi Qian 1 4 8
Affiliations

Affiliations

  • 1 Medical Research Council Centre for Reproductive Health, College of Medicine and Veterinary Medicine, Queen's Medical Research Institute, The University of Edinburgh, Edinburgh, UK.
  • 2 Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, New York, NY.
  • 3 Medical Research Council Centre for Inflammation Research, College of Medicine and Veterinary Medicine, Queen's Medical Research Institute, The University of Edinburgh, Edinburgh, UK.
  • 4 Edinburgh Cancer Research UK Centre, Institute of Genetics & Molecular Medicine, University of Edinburgh, Edinburgh, UK.
  • 5 Shanghai Jiao Tong University Affiliated Sixth People`s Hospital, Shanghai, China.
  • 6 Ministry of Education/National Health Commission/Chinese Academy of Medical Sciences Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
  • 7 Department of Orthopaedics, Centre for Orthopaedic Research, Orthopaedics Research Institute of Zhejiang University, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, China.
  • 8 Guangdong Provincial Education Department Key Laboratory of Nano-immunoregulation Tumor Microenvironment, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
PMID: 32780802 DOI: 10.1084/jem.20191820
Abstract

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.

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