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Monocyte-derived macrophages promote breast cancer bone metastasis outgrowth

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Abstract

Bone metastasis is the major cause of death in breast cancer. The lack of effective treatment suggests that the underlying mechanism of bone metastasis outgrowth is still largely unknown. As a key component of tumour microenvironment, macrophages promote tumour progression and metastasis.
In the current 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 level of CD204 and IL4R. Furthermore, monocyte/macrophage restricted
IL4R ablation significantly inhibited bone metastasis growth and IL4R-/- monocytes fail 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 for breast cancer bone disease.

ID: 149115018