Schematic of the metastic process. (i) Vascularization of growing tumor, Soluble growth factors and cytokines released from cancer cells activate endothelial cells (yellow), resulting in pericyte (green) detachment, basement membrane degradation, and endothelial sprouting. (ii) Intravasation of invasive cancer cells. Cancer cells expressing invasive phenotypes (purple) squeeze through the endothelial cells and enter the circulation. (iii) Circulating tumor cells (CTCs) traveling to a distant tissue. (iv) Extravasation of CTCs and colonization. Various factors induce CTCs to adhere to the vascular wall of a distant organ and enter its stroma. If the microenvironment is suitable for the cancer cells, they proliferate and colonize the organ, Figure not drawn to scale.