Periostin antisense oligonucleotide suppresses bleomycin-induced formation of a lung premetastatic niche for melanoma

Cancer Science
Takashi SembaHideyuki Saya

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 mel...Continue Reading

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Citations

May 5, 2020·Journal of Gastroenterology and Hepatology·Tomoki KobayashiSusumu Tazuma
Aug 20, 2019·Metabolomics : Official Journal of the Metabolomic Society·Chan SeoMan-Jeong Paik
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Mar 21, 2020·Cancer Research·Casimiro GerarduzziElliot Drobetsky
Sep 5, 2021·Trends in Cell Biology·Sarah K Deasy, Neta Erez

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Methods Mentioned

BETA
antisense oligonucleotide
antisense oligonucleotides

Software Mentioned

HistoQuest
GraphPad Prism

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