Fig. 3

Formation of the pre-metastatic bone microenvironment, rise of osteotropic breast cancer cells, dormancy of cancer cells in the perivascular microenvironment. a Breast cancer cells secrete miRNA, IL-1β, and extracellular vesicles to promote the formation of the pre-metastatic microenvironment. b The tumor stroma of breast cancer selects bone-metastatic prone cancer cells expressing CXCR4, IGF1R, and high Src activity through CXCL12 and IGF1. c The perivascular microenvironment regulates the dormancy of breast cancer cells. Endothelial cells express TSP-1 to promote the dormancy of breast cancer cells. Mesenchymal stem cells deliver extracellular vesicles to induce dormancy in breast cancer cells. d Sprouting blood vessels produce periostin, TGF-β, and reduced secretion of TSP-1, stimulating the proliferation of breast cancer cells