Adipokines, adiposity, and bone marrow adipocytes: Dangerous accomplices in multiple myeloma

Morris, Emma V.; Edwards, Claire

doi:10.1002/jcp.26884

Cited by 45 publications

(31 citation statements)

References 68 publications

(100 reference statements)

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“…BMAT is crucial in the development of blood disease, in which BMAs directly interact with blood tumour cells in the bone marrow. In addition, BMAT has been identified as a key driver in the progression of multiple myeloma [1,18,19].…”

Section: Bone Marrow Adipose Tissue (Bmat) the Third Fat Depotmentioning

confidence: 99%

Leptin, Adiponectin, and Sam68 in Bone Metastasis from Breast Cancer

Maroni

2020

IJMS

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The most serious aspect of neoplastic disease is the spread of cancer cells to secondary sites. Skeletal metastases can escape detection long after treatment of the primary tumour and follow-up. Bone tissue is a breeding ground for many types of cancer cells, especially those derived from the breast, prostate, and lung. Despite advances in diagnosis and therapeutic strategies, bone metastases still have a profound impact on quality of life and survival and are often responsible for the fatal outcome of the disease. Bone and the bone marrow environment contain a wide variety of cells. No longer considered a passive filler, bone marrow adipocytes have emerged as critical contributors to cancer progression. Released by adipocytes, adipokines are soluble factors with hormone-like functions and are currently believed to affect tumour development. Src-associated in mitosis of 68 kDa (Sam68), originally discovered as a protein physically associated with and phosphorylated by c-Src during mitosis, is now recognised as an important RNA-binding protein linked to tumour onset and progression of disease. Sam68 also regulates splicing events and recent evidence reports that dysregulation of these events is a key step in neoplastic transformation and tumour progression. The present review reports recent findings on adipokines and Sam68 and their role in breast cancer progression and metastasis.

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Section: Bone Marrow Adipose Tissue (Bmat) the Third Fat Depotmentioning

confidence: 99%

Leptin, Adiponectin, and Sam68 in Bone Metastasis from Breast Cancer

Maroni

2020

IJMS

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“…systemic chronic inflammation associated with obesity, increased bone marrow adiposity of the MM microenvironment may directly fuel MM progression [7].…”

Section: Competing Interestsmentioning

confidence: 99%

Concurrent lipidomics and proteomics on malignant plasma cells from multiple myeloma patients: Probing the lipid metabolome

et al. 2020

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Background Multiple myeloma (MM) is a hematological malignancy characterized by the clonal expansion of malignant plasma cells. Though durable remissions are possible, MM is considered incurable, with relapse occurring in almost all patients. There has been limited data reported on the lipid metabolism changes in plasma cells during MM progression. Here, we evaluated the feasibility of concurrent lipidomics and proteomics analyses from patient plasma cells, and report these data on a limited number of patient samples, demonstrating the feasibility of the method, and establishing hypotheses to be evaluated in the future. Methods Plasma cells were purified from fresh bone marrow aspirates using CD138 microbeads. Proteins and lipids were extracted using a bi-phasic solvent system with methanol, methyl tertbutyl ether, and water. Untargeted proteomics, untargeted and targeted lipidomics were performed on 7 patient samples using liquid chromatography-mass spectrometry. Two comparisons were conducted: high versus low risk; relapse versus newly diagnosed. Proteins and pathways enriched in the relapsed group was compared to a public transcriptomic dataset from Multiple Myeloma Research Consortium reference collection (n = 222) at gene and pathways level.

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“…Recently, BMAT has been shown to support cancer bone metastasis and drug resistance. (10) Emerging epidemiological studies have shown an association between obesity and MM . A meta‐analysis of prospective cohorts has shown an association between a high incidence of MM and being overweight; obesity is a poor prognostic factor for myeloma disease .…”

Section: Bone Marrow Adipose Tissuementioning

confidence: 99%

Multiple Myeloma and Fatty Acid Metabolism

et al. 2019

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Multiple myeloma (MM) accounts for 13% to 15% of all blood cancers and is characterized by the proliferation of malignant cells within the bone marrow (BM). Despite important advances in treatment, most patients become refractory and relapse with the disease. As MM tumors grow in the BM, they disrupt hematopoiesis, create monoclonal protein spikes in the blood, initiate systemic organ and immune system shutdown, and induce painful osteolytic lesions caused by overactive osteoclasts and inhibited osteoblasts. MM cells are also extremely dependent on the BM niche, and targeting the BM niche has been clinically transformative for inhibiting the positive‐feedback “vicious cycle” between MM cells and osteoclasts that leads to bone resorption and tumor proliferation. Bone marrow adipocytes (BMAs) are dynamic, secretory cells that have complex effects on osteoblasts and tumor cells, but their role in modifying the MM cell phenotype is relatively unexplored. Given their active endocrine function, capacity for direct cell–cell communication, correlation with aging and obesity (both MM risk factors), potential roles in bone disease, and physical proximity to MM cells, it appears that BMAs support MM cells. This supposition is based on research from many laboratories, including our own. Therapeutically targeting the BMA may prove to be equally transformative in the clinic if the pathways through which BMAs affect MM cells can be determined. In this review, we discuss the potential for BMAs to provide free fatty acids to myeloma cells to support their growth and evolution. We highlight certain proteins in MM cells responsible for fatty acid uptake and oxidation and discuss the potential for therapeutically targeting fatty acid metabolism or BMAs from where they may be derived. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research

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Adipokines, adiposity, and bone marrow adipocytes: Dangerous accomplices in multiple myeloma

Cited by 45 publications

References 68 publications

Leptin, Adiponectin, and Sam68 in Bone Metastasis from Breast Cancer

Leptin, Adiponectin, and Sam68 in Bone Metastasis from Breast Cancer

Concurrent lipidomics and proteomics on malignant plasma cells from multiple myeloma patients: Probing the lipid metabolome

Multiple Myeloma and Fatty Acid Metabolism

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