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Hypoxia and Bone Metastatic Disease

  • Cancer-induced Musculoskeletal Diseases (M Reagan and E Keller, Section Editors)
  • Published:
Current Osteoporosis Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

This review highlights our current knowledge of oxygen tensions in the bone marrow, and how low oxygen tensions (hypoxia) regulate tumor metastasis to and colonization of the bone marrow.

Recent Findings

The bone marrow is a relatively hypoxic microenvironment, but oxygen tensions fluctuate throughout the marrow cavity and across the endosteal and periosteal surfaces. Recent advances in imaging have made it possible to better characterize these fluctuations in bone oxygenation, but technical challenges remain. We have compiled evidence from multiple groups that suggests that hypoxia or hypoxia inducible factor (HIF) signaling may induce spontaneous metastasis to the bone and promote tumor colonization of bone, particularly in the case of breast cancer dissemination to the bone marrow.

Summary

We are beginning to understand oxygenation patterns within the bone compartment and the role for hypoxia and HIF signaling in tumor cell dissemination to the bone marrow, but further studies are warranted.

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Acknowledgements

The authors wish to acknowledge Ms. Lauren Holtslander for the graphic design in Fig. 1. This manuscript was supported by R00CA194198 (RWJ) and CA67166, CA198291, and CA197713 (AJG).

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Authors and Affiliations

  1. Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA

    Rachelle W. Johnson

  2. Department of Cancer Biology, Vanderbilt University, Nashville, TN, 37232, USA

    Rachelle W. Johnson & Miranda E. Sowder

  3. Vanderbilt Center for Bone Biology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA

    Rachelle W. Johnson & Miranda E. Sowder

  4. Department of Radiation Oncology, Division of Radiation and Cancer Biology, Stanford University, Stanford, CA, 94305, USA

    Amato J. Giaccia

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  1. Rachelle W. Johnson
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Correspondence to Rachelle W. Johnson.

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Miranda Sowder, Rachelle Johnson, and Amato Giaccia declare no conflicts of interests.

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This article is part of the Topical Collection on Cancer-induced Musculoskeletal Diseases

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Johnson, R.W., Sowder, M.E. & Giaccia, A.J. Hypoxia and Bone Metastatic Disease. Curr Osteoporos Rep 15, 231–238 (2017). https://doi.org/10.1007/s11914-017-0378-8

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