論文 - 詳細
| RRC ID | 44344 |
|---|---|
| 著者 | Sato K, Lee JW, Sakamoto K, Iimura T, Kayamori K, Yasuda H, Shindoh M, Ito M, Omura K, Yamaguchi A. |
| タイトル | RANKL synthesized by both stromal cells and cancer cells plays a crucial role in osteoclastic bone resorption induced by oral cancer. |
| ジャーナル | Am J Pathol |
| Abstract |
The molecular mechanisms underlying bone destruction by invading oral cancer are not well understood. Using IHC, we demonstrated that receptor activator of nuclear factor-κB ligand (RANKL)-positive fibroblasts and cancer cells were located at sites of bone invasion in human oral cancers. HSC3 and HO-1-N-1, human oral cancer cell lines, expressed RANKL and stimulated Rankl expression in the UAMS-32 murine osteoblastic cell line. We discriminated the roles of RANKL synthesized by stromal cells and cancer cells in cancer-associated bone resorption by using species-specific RANKL antibodies against murine RANKL and human RANKL, respectively. Osteoclastogenesis induced by the conditioned medium of HSC3 and HO-1-N-1 cells in a co-culture of murine bone marrow cells and UAMS-32 cells was inhibited by the addition of antibodies against either mouse or human RANKL. HSC3-induced bone destruction was greatly inhibited by the administration of anti-mouse RANKL antibody in a xenograft model. HO-1-N-1-induced bone destruction was inhibited by the administration of either anti-mouse or anti-human RANKL antibody. Bone destruction induced by the transplantation of human RANKL-overexpressing cells (HSC3-R2) was greatly inhibited by the injection of anti-human RANKL antibody. The present study revealed that RANKL produced by both stromal and cancer cells is involved in oral cancer-induced osteoclastic bone resorption. These results provide important information for understanding the cellular and molecular basis of cancer-associated bone destruction and the mechanism of action underlying RANKL antibody (denosumab) therapy. |
| 巻・号 | 182(5) |
| ページ | 1890-9 |
| 公開日 | 2013-5-1 |
| DOI | 10.1016/j.ajpath.2013.01.038 |
| PII | S0002-9440(13)00125-9 |
| PMID | 23499553 |
| MeSH | Animals Antibodies / pharmacology Bone Marrow Cells / drug effects Bone Marrow Cells / metabolism Bone Resorption / etiology* Bone Resorption / metabolism Bone Resorption / pathology* Cell Line, Tumor Coculture Techniques Gene Expression Regulation, Neoplastic / drug effects Humans Mice Mouth Neoplasms / complications* Mouth Neoplasms / genetics Mouth Neoplasms / pathology* Neoplasm Invasiveness Osteoclasts / drug effects Osteoclasts / metabolism Osteoclasts / pathology* Osteogenesis / drug effects Osteogenesis / genetics Osteoprotegerin / metabolism RANK Ligand / biosynthesis* RANK Ligand / genetics Stromal Cells / metabolism Stromal Cells / pathology Xenograft Model Antitumor Assays |
| IF | 3.491 |
| 引用数 | 12 |
| WOS 分野 | PATHOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | RAW 264(RCB0535) ST2(RCB0224) |