Myeloma-Modified Adipocytes Exhibit Metabolic Dysfunction and a Senescence-Associated Secretory Phenotype.

Cancer Research
Heather FairfieldMichaela R Reagan

Abstract

Bone marrow adipocytes (BMAd) have recently been implicated in accelerating bone metastatic cancers, such as acute myelogenous leukemia and breast cancer. Importantly, bone marrow adipose tissue (BMAT) expands with aging and obesity, two key risk factors in multiple myeloma disease prevalence, suggesting that BMAds may influence and be influenced by myeloma cells in the marrow. Here, we provide evidence that reciprocal interactions and cross-regulation of myeloma cells and BMAds play a role in multiple myeloma pathogenesis and treatment response. Bone marrow biopsies from patients with multiple myeloma revealed significant loss of BMAT with myeloma cell infiltration of the marrow, whereas BMAT was restored after treatment for multiple myeloma. Myeloma cells reduced BMAT in different preclinical murine models of multiple myeloma and in vitro using myeloma cell-adipocyte cocultures. In addition, multiple myeloma cells altered adipocyte gene expression and cytokine secretory profiles, which were also associated with bioenergetic changes and induction of a senescent-like phenotype. In vivo, senescence markers were also increased in the bone marrow of tumor-burdened mice. BMAds, in turn, provided resistance to dexamethasone-induced ...Continue Reading

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Citations

Jan 9, 2021·Biomarker Research·Qi WuShengrong Sun
Jan 28, 2021·Cancers·Michaela R ReaganClifford J Rosen
Apr 17, 2021·British Journal of Cancer·Abbas JafariMichaela R Reagan
May 5, 2021·Developmental Cell·Lindsay A BroadfieldSarah-Maria Fendt
May 20, 2021·Best Practice & Research. Clinical Endocrinology & Metabolism·Emma V Morris, Claire M Edwards
Aug 3, 2021·Frontiers in Endocrinology·Erica L SchellerBeata Lecka-Czernik
Jul 29, 2021·Current Osteoporosis Reports·Jessica Whitburn, Claire M Edwards

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