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) |