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Adipose, Bone, and Myeloma: Contributions from the Microenvironment

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Abstract

Researchers globally are working towards finding a cure for multiple myeloma (MM), a destructive blood cancer diagnosed yearly in ~750,000 people worldwide (Podar et al. in Expert Opin Emerg Drugs 14:99–127, 2009). Although MM targets multiple organ systems, it is the devastating skeletal destruction experienced by over 90 % of patients that often most severely impacts patient morbidity, pain, and quality of life. Preventing bone disease is therefore a priority in MM treatment, and understanding how and why myeloma cells target the bone marrow (BM) is fundamental to this process. This review focuses on a key area of MM research: the contributions of the bone microenvironment to disease origins, progression, and drug resistance. We describe some of the key cell types in the BM niche: osteoclasts, osteoblasts, osteocytes, adipocytes, and mesenchymal stem cells. We then focus on how these key cellular players are, or could be, regulating a range of disease-related processes spanning MM growth, drug resistance, and bone disease (including osteolysis, fracture, and hypercalcemia). We summarize the literature regarding MM-bone cell and MM-adipocyte relationships and subsequent phenotypic changes or adaptations in MM cells, with the aim of providing a deeper understanding of how myeloma cells grow in the skeleton to cause bone destruction. We identify avenues and therapies that intervene in these networks to stop tumor growth and/or induce bone regeneration. Overall, we aim to illustrate how novel therapeutic target molecules, proteins, and cellular mediators may offer new avenues to attack this disease while reviewing currently utilized therapies.

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Acknowledgments

The authors thank Dr. Michael Erard, Scientific Editor and Writing consultant at Maine Medical Center Research Institute (MMCRI) for editorial assistance and Dr. Clifford Rosen (MMCRI) for his expertise in Marrow Adipose. Dr. Reagan’s lab is supported by MMCRI Start-up funds, a pilot project grant from NIH/NIGMS (P30GM106391), and the NIH/NIDDK (R24 DK092759-01). Dr. Michelle McDonald is supported by The Kay Stubbs Cancer Council NSW Project Grant RG 16-03.

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Authors and Affiliations

  1. Garvan Institute of Medical Research, 384 Victoria Street, Sydney, NSW, 2010, Australia

    Michelle M. McDonald

  2. St. Vincent’s Clinical School, Faculty of Medicine, UNSW Australia, Sydney, NSW, 2010, Australia

    Michelle M. McDonald

  3. Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME, 04074, USA

    Heather Fairfield, Carolyne Falank & Michaela R. Reagan

  4. School of Medicine, Tufts University, Boston, MA, USA

    Michaela R. Reagan

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  1. Michelle M. McDonald
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  2. Heather Fairfield
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  3. Carolyne Falank
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  4. Michaela R. Reagan
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Correspondence to Michelle M. McDonald or Michaela R. Reagan.

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Michelle McDonald, Heather Fairfield, Carolyne Falank, Michaela R. Reagan are no potential conflicts of interest to disclose.

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McDonald, M.M., Fairfield, H., Falank, C. et al. Adipose, Bone, and Myeloma: Contributions from the Microenvironment. Calcif Tissue Int 100, 433–448 (2017). https://doi.org/10.1007/s00223-016-0162-2

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