fps-zm1 and Head-and-Neck-Neoplasms

Bone destruction of maxillary and mandibular bone by invasive oral squamous cell cancer (OSCC) raises various problems in the management of patients, resulting in poor outcomes and survival. However, the mechanism behind bone destruction by OSCC remains unclear. High-mobility group box 1 (HMGB1), a highly conserved ubiquitous nuclear non-histone DNA-binding protein, has been demonstrated to be secreted by aggressive cancers and regulate osteoclastogenesis, a central player during bone destruction. We therefore reasoned that HMGB1 secreted by OSCCs contributes to bone destruction. Our results showed that HMGB1 is produced by human cell lines of OSCC and promotes osteoclastogenesis via up-regulation of the expression of receptor activator of nuclear factor kappa-Β ligand in osteoblasts and osteocytes, and consequently osteoclastic bone destruction in mice. Further, we found that these actions of HMGB1 are mediated via the receptor for advanced glycation end products and toll-like receptors. These findings suggest that HMGB1 of OSCC and its down-stream signal pathways are potential targets for the treatment of bone destruction associated with advanced OSCC.

Topics: Animals; Benzamides; Bone and Bones; Bone Resorption; Cell Line, Tumor; Cell Proliferation; Disease Models, Animal; Head and Neck Neoplasms; HMGB1 Protein; Humans; Ki-67 Antigen; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Invasiveness; Osteoblasts; Osteocytes; Osteogenesis; RANK Ligand; RAW 264.7 Cells; Receptor for Advanced Glycation End Products; Squamous Cell Carcinoma of Head and Neck; Sulfonamides; Toll-Like Receptor 4