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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 tumour 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 localising along the tumour-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 down-regulate adiponectin specifically in a model of BMAds, but not in white adipocytes. The ability of myeloma cells to down-regulate adiponectin was dependent at least in part on tumour-derived TNF-alpha. Collectively our data support the link between increased bone marrow adiposity and myeloma progression. By demonstrating how myeloma cells release TNF-alpha to down-regulate BMAd-derived adiponectin, we reveal a new mechanism by which myeloma cells alter the bone microenvironment to support disease progression. This article is protected by copyright. All rights reserved.

Original publication

DOI

10.1002/jbmr.3951

Type

Journal article

Journal

J Bone Miner Res

Publication Date

30/12/2019

Keywords

adipocyte, adiponectin, bone marrow adipose tissue, cancer, multiple myeloma