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Myeloma-modified 3T3-L1 adipocytes exhibit aberrant gene expression profiles

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE143269 | GEO | 2020/11/01

REPOSITORIES: GEO

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Myeloma-modified 3T3-L1 adipocytes exhibit aberrant gene expression profiles [experiment 2]

Project description:Herein we compare mouse 3T3-L1 adipocyte gene expression after 7 days of adipogenic differentiation with and without exposure to MM.1S myeloma cells. Microarray analysis was used to compare adipogenic gene expression either following exposure to MM.1S cells prior to differentiation (48h) or after differentiation (72h).

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Myeloma-modified adipocytes exhibit a senescent-associated secretory phenotype

Project description:Bone marrow -adipocytes (BMAs) have recently been implicated in accelerating bone metastatic cancers such as AML and breast cancer. Importantly, bone marrow adipose tissue (BMAT) expands with aging and obesity- two key risk factors in multiple myeloma (MM) disease prevalence- suggesting that BMAs influence and are influenced by myeloma cells in the marrow. Here we examined how myeloma cells affect adipocytes and provide evidence that MM cells alter adipocyte gene expression and cytokine secretion profiles, creating a “MM-associated” adipocyte (MM-adipocyte) phenotype. Our findings indicate that: (1) Multiple myeloma cells decrease BM adiposity in vitro, in myeloma animal models, and in clinical samples, (2) myeloma induces widespread gene expression and phenotypic changes in adipocytes in vitro, most notable, the induction of a senescent-like phenotype in BMAs, (3) MM-adipocytes affect myeloma cell cycle, drug sensitivity, and aggressiveness, illuminating a new driver of MM cell evolution in a drug resistant clone. We demonstrate that myeloma cells exposed to MM-adipocytes are rescued from dexamethasone-induced cell cycle arrest and have increased expression of FKBP5, a potential drug resistance gene. Our findings in patients confirm that BMAs are dynamic during myeloma disease progression (decrease during MM initiation, recover during disease remission) and that the interactions between BMAs and MM cells have previously unappreciated implications in the understanding and treatment of myeloma.

2021-03-10 | GSE140374 | GEO