[摘要]：Background: Gingival squamous cell carcinoma (SCC) cells frequently invade mandibular bone, and this destruction is associated with a worse prognosis. However, the relationship between bone destruction and associated factors is unclear. In this study, the role and diagnostic utility of transforming growth factor-beta (TGF-beta) type I receptor (T beta RI) in bone destruction of the mandible was investigated. Patients and Methods: The expression of T beta RI was explored by using an immunohistochemical method on paraffin-embedded tissues from 21 cases of mandibular SCC. An inhibitor of the kinase activity of the T beta RI (T beta RI-I) was used to assess the role of T beta RI in bone destruction by a human oral SCC cell line (HSC-2) that highly expresses,T beta RI. Results: T beta RI-positive signals were closely associated with destructive invasion of the mandible by oral SCC cells. Consistent with these results, T beta RI-I greatly reduced HSC-2 cell-induced bone destruction and osteoclast formation in vivo and in vitro. T beta RI-I treatment reduced the expression of TNF-alpha, RANKL and connective tissue growth factor (CTGF/CCN2), all of which were up-regulated by TGF-beta in HSC-2 cells. Conclusion: These data demonstrated an important role for TGF-beta signalling in bone invasion by oral SCC cells, and suggest that the bone destruction is mediated by RANKL, TNF-alpha and CCN2.
