VCAN and central nervous system cancer: In addition to versican ligands, TLR2-expressing microglia are also activated by glioma-released mediators, such as HMGB1 (high mobility group protein B1), HSP (heat shock protein), and hyaluronic acid stimulation leading to MT1-MMP upregulation, enhancing ECM restructuring which in turn enhances TLR2 signaling, ultimately promoting glioma expansion and invasion, constituting a vicious circle of microglia-glioma crosstalk (137).