Research Papers:

This article has been retracted. Retraction in: Oncotarget. 2022; 13:551-552.

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 and Kenji Kangawa

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Oncotarget. 2017; 8:65534-65547. https://doi.org/10.18632/oncotarget.18032

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Takashi Nojiri1,2,*, Miki Arai3,4,*, Yutaka Suzuki4, Motofumi Kumazoe1, Takeshi Tokudome1, Koichi Miura1, Jun Hino1, Hiroshi Hosoda5, Mikiya Miyazato1, Meinoshin Okumura2, Shinpei Kawaoka3,6 and Kenji Kangawa1

1Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, Suita-City, Osaka, Japan

2Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Suita-City, Osaka, Japan

3Advanced Telecommunications Research Institute International (ATR), The Thomas N. Sato BioMEC-X Laboratories, Kyoto, Japan

4The University of Tokyo, Graduate School of Frontier Science, Kashiwa, Japan

5Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center Research Institute, Suita-City, Osaka, Japan

6ERATO Sato Live Bio-Forecasting Project, Japan Science and Technology Agency, Kyoto, Japan

*These authors contributed equally to this work and are co-first authors

Correspondence to:

Takashi Nojiri, email: [email protected]

Kenji Kangawa, email: [email protected]

Shinpei Kawaoka, email: [email protected]

Keywords: cancer metastasis, pre-metastatic niche, atrial natriuretic peptide, vascular endothelial cells, RNA-seq analyses

Received: February 08, 2017     Accepted: May 10, 2017     Published: May 25, 2017


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.

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