Macrophages orchestrate breast cancer early dissemination and metastasis.

ABSTRACT: Cancer cell dissemination during very early stages of breast cancer proceeds through poorly understood mechanisms. Here we show, in a mouse model of HER2⁺ breast cancer, that a previously described sub-population of early-evolved cancer cells requires macrophages for early dissemination. Depletion of macrophages specifically during pre-malignant stages reduces early dissemination and also results in reduced metastatic burden at end stages of cancer progression. Mechanistically, we show that, in pre-malignant lesions, CCL2 produced by cancer cells and myeloid cells attracts CD206⁺/Tie2⁺ macrophages and induces Wnt-1 upregulation that in turn downregulates E-cadherin junctions in the HER2⁺ early cancer cells. We also observe macrophage-containing t

SUBMITTER: Linde N 

PROVIDER: S-EPMC5750231 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature