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Reflections on Cancer in the Bone Marrow: Adverse Roles of Adipocytes.

ABSTRACT: This review highlights the recent advances in our understanding of adipocyte contributions to carcinogenesis or cancer disease progression for cancers in the bone. Purpose:In this review, we aim to describe bone marrow adipose tissue and discuss the soluble adipocyte-derived cytokines (adipokines) or endocrine factors, adipocyte-derived lipids, and the actual or putative juxtacrine signaling between bone marrow adipocytes and tumor cells in the bone marrow. This relationship likely affects tumor cell initiation, proliferation, metastasis, and/or drug resistance. Recent Findings:Bone marrow adipose may affect tumor proliferation, drug resistance, or cancer-induced bone disease and hence may be a new target in the fight against cancer. Summary:Overall, evidence is mixed regarding the role of bone marrow adipose and adipocytes in cancer progression, and more research in this arena is necessary to determine how these bone marrow microenvironmental cells contribute to malignancies in the marrow to identify novel, potentially targetable pathways.

SUBMITTER: Falank C

PROVIDER: S-EPMC5791905 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Reflections on Cancer in the Bone Marrow: Adverse Roles of Adipocytes.

Falank Carolyne C Fairfield Heather H Reagan Michaela R MR

Current molecular biology reports 20171019 4

This review highlights the recent advances in our understanding of adipocyte contributions to carcinogenesis or cancer disease progression for cancers in the bone.<h4>Purpose</h4>In this review, we aim to describe bone marrow adipose tissue and discuss the soluble adipocyte-derived cytokines (adipokines) or endocrine factors, adipocyte-derived lipids, and the actual or putative juxtacrine signaling between bone marrow adipocytes and tumor cells in the bone marrow. This relationship likely affect ...[more]

PMID: 29399440

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Project description:BackgroundSystemic inflammation is the main factor underlying secondary osteoporosis in patients with rheumatoid arthritis (RA). Janus kinase inhibitors (JAKi), such as tofacitinib (Tofa), can control systemic inflammation and may have beneficial effects on bone in various models. This might be due to direct effects on the bone microenvironment and not exclusively based on their anti-inflammatory function. Bone marrow adipocytes (BMAds) are abundant in the bone microenvironment. The effect of JAKi on BMAds is unknown, but evidence suggests that there is competition between human bone marrow-derived stromal cell (hBMSC) differentiation routes towards BMAds and osteoblasts (Ob) in osteoporosis.ObjectivesThe aims of the study are to determine whether Tofa influences BMAds and Ob derived from hBMSCs and to investigate the potential effects of Tofa on bone marrow adiposity in RA patients.MethodsTo determine the effect of Tofa on cellular commitment, hBMSCs were differentiated to BMAds or OBs for 3 days together with Tofa at 200, 400, or 800 nM and TNFα. This study was also conducted using differentiated BMAds. The impact of Tofa was determined by gene and protein expression analysis and cell density monitoring. In parallel, in a pilot study of 9 RA patients treated with Tofa 5 mg twice a day (NCT04175886), the proton density fat fraction (PDFF) was measured using MRI at the lumbar spine at baseline and at 6 months.ResultsIn non-inflammatory conditions, the gene expression of Runx2 and Dlx5 decreased in Ob treated with Tofa (p <0.05). The gene expression of PPARγ2, C/EBPα, and Perilipin 1 were increased compared to controls (p <0.05) in BMAds treated with Tofa. Under inflammatory conditions, Tofa did not change the expression profiles of Ob compared to TNFα controls. In contrast, Tofa limited the negative effect of TNFα on BMAd differentiation (p <0.05). An increase in the density of differentiated BMAds treated with Tofa under TNFα was noted (p <0.001). These findings were consolidated by an increase in PDFF at 6 months of treatment with Tofa in RA patients (46.3 ± 7.0% versus 53.2 ± 9.2% p <0.01).ConclusionTogether, these results suggest a stimulatory effect of Tofa on BMAd commitment and differentiation, which does not support a positive effect of Tofa on bone.

Dataset Information

Reflections on Cancer in the Bone Marrow: Adverse Roles of Adipocytes.

Publications

Reflections on Cancer in the Bone Marrow: Adverse Roles of Adipocytes.

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