Fig. 8 | Nature Communications

Fig. 8

From: Macrophages orchestrate breast cancer early dissemination and metastasis

Fig. 8

Models summarizing findings and potential scenarios for early DCC role in metastasis development. a Scheme of macrophage-regulated early dissemination from pre-invasive lesions where CCR2+/CD206hi/F4/80hi/Tie2hi macrophages are attracted into early lesions by HER2-mediated and NF-κB-mediated upregulation of CCL2. Our models support that intra-epithelial macrophages in turn secrete Wnt-1 in response to CCL2 production by cancer cells and also other immune cells and thereby further cement an EMT-like response that is also stimulated by autocrine/paracrine production of other Wnt ligands8, 9 to drive early dissemination. b Early DCCs contribute to metastasis formation, either as a slow cycling seeds of metastasis (scenario 1) or by interacting with the microenvironment and/or later arriving DCCs to create a “pre-metastatic niche” that is eDCC-orchestrated and more permissive for the growth of late or early and late cancer cells (scenario 2)