論文 - 詳細
| RRC ID | 55938 |
|---|---|
| 著者 | Semba T, Sugihara E, Kamoshita N, Ueno S, Fukuda K, Yoshino M, Takao K, Yoshikawa K, Izuhara K, Arima Y, Suzuki M, Saya H. |
| タイトル | Periostin antisense oligonucleotide suppresses bleomycin-induced formation of a lung premetastatic niche for melanoma. |
| ジャーナル | Cancer Sci |
| Abstract |
Metastasis is the leading cause of cancer death. A tumor-supportive microenvironment, or premetastatic niche, at potential secondary tumor sites plays an important role in metastasis, especially in tumor cell colonization. Although a fibrotic milieu is known to promote tumorigenesis and metastasis, the underlying molecular contributors to this effect have remained unclear. Here we show that periostin, a component of the extracellular matrix that functions in tissue remodeling, has a key role in formation of a fibrotic environment that promotes tumor metastatic colonization. We found that periostin was widely expressed in fibrotic lesions of mice with bleomycin-induced lung fibrosis, and that up-regulation of periostin expression coincided with activation of myofibroblasts positive for α-smooth muscle actin. We established a lung metastasis model for B16 murine melanoma cells and showed that metastatic colonization of the lung by these cells was markedly promoted by bleomycin-induced lung fibrosis. Inhibition of periostin expression by giving an intratracheal antisense oligonucleotide targeting periostin mRNA was found to suppress bleomycin-induced lung fibrosis and thereby to attenuate metastatic colonization of the lung by melanoma cells. Our results indicate that periostin is a key player in the development of bleomycin-induced fibrosis and consequent enhancement of tumor cell colonization in the lung. Our results therefore implicate periostin as a potential target for prevention or treatment of lung metastasis. |
| 巻・号 | 109(5) |
| ページ | 1447-1454 |
| 公開日 | 2018-5-1 |
| DOI | 10.1111/cas.13554 |
| PMID | 29498146 |
| PMC | PMC5980369 |
| MeSH | Actins / metabolism Animals Bleomycin / adverse effects* Cell Adhesion Molecules / antagonists & inhibitors* Cell Adhesion Molecules / genetics Cell Line, Tumor Extracellular Matrix / metabolism Lung Neoplasms / genetics Lung Neoplasms / metabolism Lung Neoplasms / pathology Lung Neoplasms / secondary* Melanoma, Experimental / genetics Melanoma, Experimental / metabolism Melanoma, Experimental / pathology* Mice Oligonucleotides, Antisense / administration & dosage* Oligonucleotides, Antisense / pharmacology Pulmonary Fibrosis / chemically induced Pulmonary Fibrosis / genetics Pulmonary Fibrosis / metabolism Pulmonary Fibrosis / therapy* Tumor Microenvironment Up-Regulation Xenograft Model Antitumor Assays |
| IF | 4.751 |
| 引用数 | 5 |
| 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 | F1000Research |
| 各媒体での言及数の合計 | 2 |
| 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 | B16 melanoma(RCB1283) B16/BL6(RCB2638) |