HMGB1 and neoplasm: After intravasation, most of tumor cells in circulation are damaged by the shear stress and mechanical stresses in blood, thus releasing intracellular molecules, many of which have been identified as the ligands for TLR2/4, including HMGB1, HSP60, HSP70, gp96, S100A8, S100A9, SAA3 and so on [48].