Figure 3

Angiogenic dormancy (“extrinsic dormancy”) at niches. At niches, dormancy can be induced through signaling between DTCs, endothelial cells, and stroma with both upregulation and downregulation of multiple factors and signaling axes. DTCs enter dormancy with a vascular structure that is stable and non-angiogenic. In contrast, a sprouting vascular structure triggers tumor cells to exit from dormancy following an “angiogenic switch” in microenvironment, leading to tumor outgrowth and recurrence or metastasis. BMP, bone morphogenetic protein; CXCL12, Chemokine (C-X-C motif) ligand 12; EGFR, epithelial growth factor receptors; ESM-1, endothelial specific marker 1; FGF, fibroblast growth factor; HSP27, heat shock protein 27; IGFBP5, insulin-like growth factor binding protein 5; LTBPs, latent transforming growth factor β binding protein; PDGF, platelet-derived growth factor; TGF-β, transforming growth factor β; VEGFs, vascular endothelial growth factors.