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Figure 4: Schematic representation of CSC participation in vasculogenic mimicry and neovascularization initiated by the presence of EPCs. Like in tumor angiogenic sprouting, neovascularization starts with the secretion of proangiogenic factors (such as VEGF) by the tumor under hypoxia. The proangiogenic factors circulate into the bloodstream towards the bone marrow, targeting the release of EPCs. The activated EPCs form a column from the existing blood vessel. PEDF has antitumor properties as an effective antiangiogenic, antiproliferative, and prodifferentiation factor.