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
リソース情報
ヒト・動物細胞 B16 melanoma(RCB1283) B16/BL6(RCB2638)