Transcriptome analysis reveals a role for the endothelial ANP-GC-A signaling in interfering with pre-metastatic niche formation by solid cancers

Takashi Nojiri, Miki Arai, Yutaka Suzuki, Motofumi Kumazoe, Takeshi Tokudome, Koichi Miura, Jun Hino, Hiroshi Hosoda, Mikiya Miyazato, Meinoshin Okumura, Shinpei Kawaoka, Kenji Kangawa

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Cancer establishes a microenvironment called the pre-metastatic niche in distant organs where disseminated cancer cells can efficiently metastasize. Pre-metastatic niche formation requires various genetic factors. Previous studies suggest that inhibiting a single niche-factor is insufficient to completely block pre-metastatic niche formation especially in human patients. Here we show that the atrial natriuretic peptide (ANP), an endogenous hormone produced by the heart, inhibits pre-metastatic niche formation and metastasis of murine solid cancer models when pharmacologically supplied in vivo. On the basis of a wealth of comprehensive RNA-seq data, we demonstrated that ANP globally suppressed expression of cancer-induced genes including known niche-factors in the lung. The lungs of mice overexpressing GC-A, a receptor for ANP in endothelial cells, were conferred resistance against pre-metastatic niche formation. Importantly, neither ANP administration nor GC-A overexpression had a detrimental effect on lung gene expression in a cancer-free condition. The current study establishes endothelial ANP-GC-A signaling as a therapeutic target to control the pre-metastatic niche.

Original languageEnglish
Pages (from-to)65534-65547
Number of pages14
JournalOncotarget
Volume8
Issue number39
DOIs
Publication statusPublished - 2017
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology

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