1. Bone destruction by invading oral squamous carcinoma cells mediated by the transforming growth factor-beta signalling pathway.
- Author
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Goda T, Shimo T, Yoshihama Y, Hassan NM, Ibaragi S, Kurio N, Okui T, Honami T, Kishimoto K, and Sasaki A
- Subjects
- Aged, Aged, 80 and over, Animals, Carcinoma, Squamous Cell genetics, Cell Line, Tumor, Connective Tissue Growth Factor biosynthesis, Connective Tissue Growth Factor genetics, Female, Gene Expression, Gingival Neoplasms genetics, Humans, Male, Mice, Mice, Nude, Middle Aged, Osteolysis genetics, Osteolysis metabolism, Protein Serine-Threonine Kinases antagonists & inhibitors, Protein Serine-Threonine Kinases biosynthesis, RANK Ligand biosynthesis, RANK Ligand genetics, Receptor, Transforming Growth Factor-beta Type I, Receptors, Transforming Growth Factor beta antagonists & inhibitors, Receptors, Transforming Growth Factor beta biosynthesis, Signal Transduction, Transforming Growth Factor beta antagonists & inhibitors, Transplantation, Heterologous, Tumor Necrosis Factor-alpha biosynthesis, Tumor Necrosis Factor-alpha genetics, Carcinoma, Squamous Cell metabolism, Carcinoma, Squamous Cell pathology, Gingival Neoplasms metabolism, Gingival Neoplasms pathology, Osteolysis pathology, Transforming Growth Factor beta metabolism
- Abstract
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 (TbetaRI) in bone destruction of the mandible was investigated., Patients and Methods: The expression of TbetaRI 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 TbetaRI (TbetaRI-I) was used to assess the role of TbetaRI in bone destruction by a human oral SCC cell line (HSC-2) that highly expresses TbetaRI., Results: TbetaRI-positive signals were closely associated with destructive invasion of the mandible by oral SCC cells. Consistent with these results, TbetaRI-I greatly reduced HSC-2 cell-induced bone destruction and osteoclast formation in vivo and in vitro. TbetaRI-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.
- Published
- 2010