Multiple sources of HMGB1 exist in the tumor microenvironment; 1) necrotic tumor cells passively release HMGB1 into the peripheral space; 2) tumor-associated macrophages (TAMs) actively secrete HMGB1 and other vascularization growth factor [62]; 3) it also has been shown that endothelial cells secrete HMGB1 after activation and re-activate themselves upon exposure to that of previously secreted HMGB1 [61]. This evidence concerns the gene HMGB1 and neoplasm.