Bone marrow adiposity and multiple myeloma

Morris, Emma V.; Edwards, Claire

doi:10.1016/j.bone.2018.03.011

Cited by 22 publications

(17 citation statements)

References 61 publications

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“…BM MSCs can differentiate into adipocytes, which increase with age and are considered negative regulators of haematopoiesis (Naveiras et al, 2009). The effects of MM on BM adipocytes remain to be elucidated (Morris & Edwards, 2018). Although adipocytes are evident in interstitial BM and support MM growth in vitro (Trotter et al, 2016;Fairfield et al, 2018), adiponectin, an adipogenic factor, has been shown to induce anti-MM activity and is suppressed in MM (Fowler et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal stem cells gene signature in high‐risk myeloma bone marrow linked to suppression of distinct IGFBP2‐expressing small adipocytes

et al. 2018

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Summary Recent studies suggest that multiple myeloma (MM) induces proliferation and expansion of bone marrow (BM) mesenchymal stem cells (MSCs), but others showed that MM cells induce MSC senescence. To clarify the interaction between MM and MSCs, we exploited our established MSC gene signature to identify gene expression changes in myeloma MSCs and associated functional differences. Single MSCs from patients with MM had changes in expression of genes associated with cellular proliferation and senescence and a higher proportion of senescent cells and lower proliferative potential than those from age‐matched healthy donors. Single MSCs from both sources heterogeneously express MSC genes associated with adipogenesis and osteoblastogenesis. We identified the gene encoding insulin‐like growth factor‐binding protein 2 (IGFBP2), an MSC gene commonly altered in high risk MM, as under‐expressed. Morphologically, IGFBP2+ cells are underrepresented in MM BM compared to smouldering MM. Strong IGFBP2 and adiponectin co‐expression was detected in a subset of small adipocytes. Co‐culturing normal MSCs with myeloma cells suppressed MSC differentiation to adipocytes and osteoblasts, and reduced expression of IGFBP2 and adiponectin. Recombinant IGFBP2 blocked IGF1‐mediated myeloma cell growth. Our data demonstrate that myeloma MSCs are less proliferative and that IGFBP2+ small adipocytes are a distinct mesenchymal cell population suppressed by myeloma.

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Section: Discussionmentioning

confidence: 99%

Mesenchymal stem cells gene signature in high‐risk myeloma bone marrow linked to suppression of distinct IGFBP2‐expressing small adipocytes

et al. 2018

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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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“…We now showed that post-treatment BM-MSC did indeed differentiate more easily into adipocytes than into osteoblasts. We notably observed that expression of leptin was down-regulated in post-treatment BM-MSC, which was also in favor of the defect in osteogenesis [34]. The ability to better differentiate into adipocytes appeared as soon as MM was diagnosed.…”

Section: Discussionmentioning

confidence: 83%

Imprinting of Mesenchymal Stromal Cell Transcriptome Persists even after Treatment in Patients with Multiple Myeloma

Lemaître

Ferreira

Joubert

et al. 2020

IJMS

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Introduction. Multiple myeloma (MM) is a B-cell neoplasm characterized by clonal expansion of malignant plasma cells (MM cells) in the bone-marrow (BM) compartment. BM mesenchymal stromal cells (MSC) from newly diagnosed MM patients were shown to be involved in MM pathogenesis and chemoresistance. The patients displayed a distinct transcriptome and were functionally different from healthy donors’ (HD) MSC. Our aim was to determine whether MM–MSC also contributed to relapse. Methods. We obtained and characterized patients’ MSC samples at diagnosis, two years after intensive treatment, without relapse and at relapse. Results. Transcriptomic analysis revealed differences in gene expression between HD and MM-MSC, whatever the stage of the disease. An easier differentiation towards adipogenesis at the expense of osteoblatogeneis was observed, even in patients displaying a complete response to treatment. Although their transcriptome was similar, we found that MSC from relapsed patients had an increased immunosuppressive ability, compared to those from patients in remission. Conclusion. We demonstrated that imprinting of MSC transcriptome demonstrated at diagnosis of MM, persisted even after the apparent disappearance of MM cells induced by treatment, suggesting the maintenance of a local context favorable to relapse.

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Bone marrow adiposity and multiple myeloma

Cited by 22 publications

References 61 publications

Mesenchymal stem cells gene signature in high‐risk myeloma bone marrow linked to suppression of distinct IGFBP2‐expressing small adipocytes

Mesenchymal stem cells gene signature in high‐risk myeloma bone marrow linked to suppression of distinct IGFBP2‐expressing small adipocytes

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

Imprinting of Mesenchymal Stromal Cell Transcriptome Persists even after Treatment in Patients with Multiple Myeloma

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