LEP and breast cancer: In breast cancer, leptin promotes angiogenesis via several mechanisms (Figure 2): i) leptin acts directly on breast cancer stroma to promote the production of soluble pro-angiogenic signals (e.g., VEGF (89), FGF); ii) leptin acts directly on ECs of tumor blood vessels to promote angiogenic activation and enhance angiogenic responses (90); and iii) leptin indirectly promotes angiogenesis by priming the tumor microenvironment for neovascularization through effects on estrogen signaling and immune cell activation.