Gfi1 expressed in bone marrow stromal cells is a novel osteoblast suppressor in patients with multiple myeloma bone disease

D'Souza, Sonia; Prete, Davide Del; Jin, Shunqian; Sun, Qi; Huston, Alissa; Kostov, Flavia Esteve; Sammut, Bénédicte; Hong, Chang Sook; Anderson, Judith H.; Patrene, Kenneth D.; Yu, Shibing; Velu, Chinavenmeni S.; Xiao, Guozhi; Grimes, H. Leighton; Roodman, G. David; Galson, Deborah L.

doi:10.1182/blood-2011-04-346775

Cited by 86 publications

(113 citation statements)

References 52 publications

(83 reference statements)

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“…TFs with the highest number of TFBS and gene hits were Elk1 [36] and Gfi1 [37] in List I; and Elk4 [36] and GABPA [38] in List II. Interestingly, in the myeloma context, Gfi1 has recently been pointed out as a new transcriptional repressor of Runx2, blocking OB differentiation and being increased both in MSCs from MM patients and MM-bearing mice [24]. Among the multiple target genes regulated by these four transcription factors, many have been reported to be critical for MM pathogenesis (Supp.…”

Section: Resultsmentioning

confidence: 99%

Transcriptomic profile induced in bone marrow mesenchymal stromal cells after interaction with multiple myeloma cells: implications in myeloma progression and myeloma bone disease

et al. 2014

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Despite evidence about the implication of the bone marrow (BM) stromal microenvironment in multiple myeloma (MM) cell growth and survival, little is known about the effects of myelomatous cells on BM stromal cells. Mesenchymal stromal cells (MSCs) from healthy donors (dMSCs) or myeloma patients (pMSCs) were co-cultured with the myeloma cell line MM.1S, and the transcriptomic profile of MSCs induced by this interaction was analyzed. Deregulated genes after co-culture common to both d/pMSCs revealed functional involvement in tumor microenvironment cross-talk, myeloma growth induction and drug resistance, angiogenesis and signals for osteoclast activation and osteoblast inhibition. Additional genes induced by co-culture were exclusively deregulated in pMSCs and predominantly associated to RNA processing, the ubiquitine-proteasome pathway, cell cycle regulation, cellular stress and non-canonical Wnt signaling. The upregulated expression of five genes after co-culture (CXCL1, CXCL5 and CXCL6 in d/pMSCs, and Neuregulin 3 and Norrie disease protein exclusively in pMSCs) was confirmed, and functional in vitro assays revealed putative roles in MM pathophysiology. The transcriptomic profile of pMSCs co-cultured with myeloma cells may better reflect that of MSCs in the BM of myeloma patients, and provides new molecular insights to the contribution of these cells to MM pathophysiology and to myeloma bone disease.

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Section: Resultsmentioning

confidence: 99%

Transcriptomic profile induced in bone marrow mesenchymal stromal cells after interaction with multiple myeloma cells: implications in myeloma progression and myeloma bone disease

et al. 2014

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“…MM cells enhance osteoclastogenesis 33,34 while suppressing osteoblastogenesis, [35][36][37][38][39] leading to devastating bone destruction with rapid loss of bone. Along with the progression of bone disease, the bone marrow microenvironment is skewed by MM cells, which underlies the unique pathophysiology of MM and confers aggressiveness and drug resistance in MM cells.…”

Section: Discussionmentioning

confidence: 99%

TAK1 inhibition subverts the osteoclastogenic action of TRAIL while potentiating its antimyeloma effects

Tenshin

Teramachi²,

Oda³

et al. 2017

Blood Advances

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Key Points• TRAIL enhances receptor activator of NF-kB ligand-induced osteoclastogenesis and c-FLIP upregulation without osteoclast apoptosis induction.• TAK1 inhibition triggers TRAIL-induced apoptosis in osteoclasts, while potentiating TRAIL-induced myeloma cell death.Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) agonists induce tumorspecific apoptosis indicating that they may be an attractive therapeutic strategy against cancers, including multiple myeloma (MM). Osteoclastogenesis is highly induced in MM,

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“…5TGM1-GFP EV or MMP-13-KD cells (1 × 10 5 cells) were bilaterally injected into both tibiae of C57BL/6 Rag2 -/-female mice as described previously (41,70). Mice were sacrificed 4 weeks later, and tibiae were collected for GFP imaging and then fixed in 4% neutral-buffered formalin for micro-qCT analysis.…”

Section: Methodsmentioning

confidence: 99%

Multiple myeloma–derived MMP-13 mediates osteoclast fusogenesis and osteolytic disease

Fu¹,

Liu²,

Feng³

et al. 2016

Journal of Clinical Investigation

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Gfi1 expressed in bone marrow stromal cells is a novel osteoblast suppressor in patients with multiple myeloma bone disease

Cited by 86 publications

References 52 publications

Transcriptomic profile induced in bone marrow mesenchymal stromal cells after interaction with multiple myeloma cells: implications in myeloma progression and myeloma bone disease

Transcriptomic profile induced in bone marrow mesenchymal stromal cells after interaction with multiple myeloma cells: implications in myeloma progression and myeloma bone disease

TAK1 inhibition subverts the osteoclastogenic action of TRAIL while potentiating its antimyeloma effects

Multiple myeloma–derived MMP-13 mediates osteoclast fusogenesis and osteolytic disease

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