Affordable Access

Publisher Website

Myeloma Cells Down-Regulate Adiponectin in Bone Marrow Adipocytes Via TNF-Alpha.

  • Morris, Emma V1, 2, 3
  • Suchacki, Karla J4
  • Hocking, Joseph2, 5
  • Cartwright, Rachel2, 5
  • Sowman, Aneka2, 5
  • Gamez, Beatriz1, 2, 3
  • Lea, Ryan2, 5
  • Drake, Matthew T6
  • Cawthorn, William P4
  • Edwards, Claire M1, 2, 3, 5
  • 1 Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
  • 2 NIHR Oxford BRC, Oxford, UK.
  • 3 Oxford Centre for Translational Myeloma Research, Oxford, UK.
  • 4 University/British Heart Foundation Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
  • 5 Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, Oxford, UK.
  • 6 Kogod Center on Aging and Division of Endocrinology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA.
Published Article
Journal of Bone and Mineral Research
Wiley (John Wiley & Sons)
Publication Date
May 01, 2020
DOI: 10.1002/jbmr.3951
PMID: 31886918


Multiple myeloma is caused by abnormal plasma cells that accumulate in the bone marrow and interact with resident cells of the bone microenvironment to drive disease progression and development of an osteolytic bone disease. Bone marrow adipocytes (BMAds) are emerging as having important endocrine functions that can support myeloma cell growth and survival. However, how BMAds respond to infiltrating tumor cells remains poorly understood. Using the C57BL/KaLwRij murine model of myeloma, bone marrow adiposity was found to be increased in early stage myeloma with BMAds localizing along the tumor-bone interface at later stages of disease. Myeloma cells were found to uptake BMAd-derived lipids in vitro and in vivo, although lipid uptake was not associated with the ability of BMAds to promote myeloma cell growth and survival. However, BMAd-derived factors were found to increase myeloma cell migration, viability, and the evasion of apoptosis. BMAds are a major source of adiponectin, which is known to be myeloma-suppressive. Myeloma cells were found to downregulate adiponectin specifically in a model of BMAds but not in white adipocytes. The ability of myeloma cells to downregulate adiponectin was dependent at least in part on TNF-α. Collectively our data support the link between increased bone marrow adiposity and myeloma progression. By demonstrating how TNF-α downregulates BMAd-derived adiponectin, we reveal a new mechanism by which myeloma cells alter the bone microenvironment to support disease progression. © 2019 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research. © 2019 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

Report this publication


Seen <100 times