UMMS Affiliation
Department of Dermatology
Publication Date
2018-05-01
Document Type
Article
Disciplines
Cancer Biology | Dermatology | Neoplasms | Skin and Connective Tissue Diseases
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 alpha-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.
Keywords
antisense oligonucleotide, lung fibrosis, melanoma, periostin, premetastatic niche
Rights and Permissions
© 2018 The Authors. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
DOI of Published Version
10.1111/cas.13554
Source
Cancer Sci. 2018 May;109(5):1447-1454. doi: 10.1111/cas.13554. Epub 2018 Mar 31. Link to article on publisher's site
Journal/Book/Conference Title
Cancer science
Related Resources
PubMed ID
29498146
Repository Citation
Semba, Takashi; Sugihara, Eiji; Kamoshita, Nagisa; Ueno, Sayaka; Fukuda, Keitaro; Yoshino, Masafumi; Takao, Kazumasa; Yoshikawa, Kazunori; Izuhara, Kenji; Arima, Yoshimi; Suzuki, Makoto; and Saya, Hideyuki, "Periostin antisense oligonucleotide suppresses bleomycin-induced formation of a lung premetastatic niche for melanoma" (2018). Open Access Articles. 3409.
https://escholarship.umassmed.edu/oapubs/3409
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License
Included in
Cancer Biology Commons, Dermatology Commons, Neoplasms Commons, Skin and Connective Tissue Diseases Commons