In bone sarcoma contexts, BDNF–TrkB signaling promotes angiogenic programs via PLCγ/PKCα and HIF−1α−dependent induction of VEGF, a change expected to alter leukocyte trafficking and the nutrient landscape within tumors; although these findings were established in human chondrosarcoma, they delineate a TrkB−centered pathway that is operative in skeletal tumors and relevant to osteosarcoma vascular phenotypes (38, 39). This evidence concerns the gene BDNF and osteosarcoma.