VEGFA and breast carcinoma: In addition to regulate bone metabolism, it is reported that ISL could induce anti-angiogenic effects, including inhibition of breast cancer neoangiogenesis via suppress vascular endothelial growth factor (VEGF)/VEGFR-2 signaling pathway and matrix metalloproteinase-2 (MMP-2)29, suppression platelet-derived growth factor-BB (PDGF-BB) which secreted by preosteoclasts induces angiogenesis during coupling with osteogenesis30.