論文 - 詳細
| RRC ID | 81287 |
|---|---|
| 著者 | Yui Y, Kumai J, Watanabe K, Wakamatsu T, Sasagawa S. |
| タイトル | Lung fibrosis is a novel therapeutic target to suppress lung metastasis of osteosarcoma. |
| ジャーナル | Int J Cancer |
| Abstract |
The prognosis of patients with metastatic and recurrent osteosarcoma has not improved over the last 30 years because no effective treatment strategy has been established for lung metastases. Although molecular-targeted drugs that modify the extracellular environment, such as antifibrotic agents, have been developed for cancer treatment, the suppressive effects of antifibrotic agents on osteosarcoma lung metastasis are unclear. Osteosarcomas need to adapt to considerable changes with respect to the stiffness of the environment and fibrosis during lung metastasis and may thus be vulnerable to fibrotic suppression as they originate at the site of a stiff bone with considerable fibrosis. In our study, we investigated whether fibrosis was a therapeutic target for suppressing osteosarcoma metastasis. Lung tissue samples from patients and a mouse model (LM8-Dunn model) showed that lung metastatic colonization of osteosarcoma cells proceeded with massive lung fibrosis. Metastatic osteosarcoma LM8 cells proliferated in a scaffold-dependent manner; the proliferation was less dependent on YAP-mediated mechanotransduction on soft polyacrylamide gels. The antifibrotic agents pirfenidone and nintedanib suppressed lung metastasis in the LM8-Dunn model. The osteosarcoma cells did not show increased proliferation, as reported in breast cancer, after continuous culture in a soft environment. We speculated that the antifibrotic agents were effective because the osteosarcoma cells remained scaffold-dependent in the soft tissue environment. Thus, antifibrotic strategies may be useful in suppressing lung metastasis of bone and soft tissue tumors with stiff primary sites such as those in osteosarcoma. |
| 巻・号 | 151(5) |
| ページ | 739-751 |
| 公開日 | 2022-9-1 |
| DOI | 10.1002/ijc.34008 |
| PMID | 35342929 |
| MeSH | Animals Bone Neoplasms* / drug therapy Bone Neoplasms* / pathology Cell Line, Tumor Lung Neoplasms* / pathology Mechanotransduction, Cellular Mice Mice, Inbred C3H Neoplasm Recurrence, Local Osteosarcoma* / pathology Pulmonary Fibrosis* |
| IF | 5.145 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 3 |
| 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 | Saos-2(RCB0428) |