Figure 2.

Mechanisms of tumor angiogenesis. Angiogenic and growth factors produced by tumor cells, hypoxia and acidosis in the tumor microenvironment promote the sequence of alternative mechanisms of angiogenesis. Trans-differentiation of cancer stem cells: proteins expressed in tumor cells induce trans-differentiation of cancer stem cells to endothelial cell-like phenotypes. Vascular mimicry: a matrix-embedded fluid-conducting meshwork formed by tumor cells. Vessel cooption: tumors gain blood supply by hijacking existing vasculature, and tumor cells migrate along the existing vessels. Sprouting angiogenesis: a process involving outgrowth of tip cells from the existing vasculature directed towards areas with a high abundance of pro-migratory growth factors released by the tumor. Intussusceptive angiogenesis: the splitting of the pre-existing vessel into two vessels. This process is characterized by the formation of ”transvascular pillars” without endothelial proliferation. BM-EPC recruitment: angiogenic and growth factors recruit, from BM, EPCs that differentiate into ECs. (EC: endothelial cell; BM: bone marrow; EPC: endothelial progenitor cell).