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Signaling Pathways Underlying Bone Metastasis: Hypoxia Signaling in Bone Metastasis and Beyond

  • Molecular Biology of Bone Metastasis (H Taipaleenmäki, Section Editor)
  • Published:
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Abstract

Purpose of Review

This review provides an overview of the mechanisms induced by hypoxia that take place within primary tumors and within the bone microenvironment, and that promote bone metastasis.

Recent Findings

In primary tumors, hypoxia stimulates metastasis by promoting vascularization, epithelial-mesenchymal transition, immunosuppression, and by inducing pre-metastatic lesions in distant tissues. In bones, local hypoxia maintains bone homeostasis and has been recently shown to promote tumor colonization, to reactivate dormant tumor cells, and strikingly, to promote systemic cancer growth and dissemination beyond the skeleton.

Summary

Hypoxia is recognized as a critical component of the tumor microenvironment that strongly affects tumor growth and metastasis. However, our knowledge of the mechanisms induced locally by hypoxia in the skeleton that promotes tumor dissemination in bones and beyond is only emerging. Recent studies identified LIFR and CXCL12 as important factors downstream of hypoxia signaling in the bone, but other molecules and mechanisms will be likely discovered in the future.

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Acknowledgements

This manuscript was supported by the Institut National de la Santé et de la Recherche Médicale (INSERM) and the Fondation ARC pour la Recherche Contre le Cancer (Project # R10081HS and C14007HS to S. Provot). The work performed by the authors cited here also received the support of the University of California San Francisco Academic Senate Committee on Research (Fund # 34935/500394 to S. Provot), and the Association le Cancer du Sein Parlons-en (Pink Ribbon award to S. Provot). C.S. Devignes was supported by the French Ministry of Research, and the Fondation ARC, and was recipient of the Société Française de Biologie des Tissus Minéralisés (SFBTM) award. The authors would like to acknowledge the investigators who generated the work highlighted in this review and to apologize for the published articles that were not cited due to space constraints.

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  1. INSERM U1132 and Paris Diderot University, Paris, France

    Claire-Sophie Devignes, Yetki Aslan & Sylvain Provot

  2. INSERM Unit 1132, Hôpital Lariboisière - Centre Viggo Petersen, 2 rue Ambroise Paré, 75010, Paris, France

    Sylvain Provot

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  1. Claire-Sophie Devignes
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Claire-Sophie Devignes, Yetki Aslan, and Sylvain Provot declare no conflicts of interest.

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This article is part of the Topical Collection on Molecular Biology of Bone Metastasis

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Devignes, CS., Aslan, Y. & Provot, S. Signaling Pathways Underlying Bone Metastasis: Hypoxia Signaling in Bone Metastasis and Beyond. Curr Mol Bio Rep 4, 69–79 (2018). https://doi.org/10.1007/s40610-018-0090-1

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