Phenotypic and functional characterization of bone marrow mesenchymal stem cells derived from patients with multiple myeloma

Arnulf, Bertrand; Lecourt, Séverine; Soulier, Jean; Ternaux, Brigitte; Lacassagne, M-Noelle; Crinquette, Antoine; Dessoly, J; Sciaini, A-K; Benbunan, M; Chomienne, Christine; Fermand, JP; Marolleau, JP; Larghero, Jérôme

doi:10.1038/sj.leu.2404466

Cited by 166 publications

(164 citation statements)

References 30 publications

Supporting

Mentioning

155

Contrasting

Unclassified

Order By: Relevance

“…Although recent studies pointed out the abnormal features of MSCs in MM patients (32,33), we thought that the BM milieu with the proliferation of myeloma cells produced abnormal characteristics of MSCs. We added 0.5-5 nM bortezomib to an osteoprogenitor cell culture based on data showing the range of IC 50 to be 2.5-30 nM when bortezomib was administered to patients with MM (14) and our preliminary result showed that 10 nM bortezomib was too cytotoxic for osteoprogenitor cells (data not shown).…”

Section: Discussionmentioning

confidence: 76%

Osteoprogenitor differentiation is not affected by immunomodulatory thalidomide analogs but is promoted by low bortezomib concentration, while both agents suppress osteoclast differentiation

Munemasa

Sakai²,

Kuroda³

et al. 2008

Int J Oncol

View full text Add to dashboard Cite

Abstract.We investigated the effects of bortezomib (PS-341) and immunomodulatory thalidomide analogs (immunomodulatory compounds; CC-4047, CC-6032, and CC-5013, or lenalidomide) on osteoblast and osteoclast differentiation in vitro using human mesenchymal stem cells (hMSC) to commit to osteoprogenitor cells and peripheral blood mononuclear cells (PBMCs) isolated from healthy donors, respectively. First, the concentration of bortezomib for an anti-myeloma effect was more than 1.0 nM in myeloma cells of multiple myeloma (MM) patients and more than 2.5 nM in myeloma cell lines. In contrast, anti-myeloma effects of immunomodulatory compounds on myeloma cells differed among myeloma cells and these compounds themselves. Subsequently, these agents (bortezomib; 0.5-5.0 nM, immunomodulatory compounds; 10 μM) were added to the osteoprogenitor cell culture media or the media for osteoclast differentiation. Low bortezomib concentrations (0.5 and 1.0 nM) increased ALP activity, and the delayed addition of bortezomib further increased ALP activity. Mineralized nodular formation with <2.5 nM bortezomib was not impaired. BMP2 expression on osteoprogenitor cells was found to increase in a time-dependent manner irrespective of treatment with bortezomib. On the other hand, the antiosteoclast effect with low bortezomib concentration (≤2.5 nM) depended on MM patients. In contrast, immunomodulatory compounds at 10 μM showed an anti-osteoclast effect without cytotoxicity to osteoblast differentiation, at which dose myeloma cells underwent apoptosis. These findings might improve the treatment strategy for MM patients without damaging BM stromal cells by combining bortezomib with immunomodulatory compounds.

show abstract

Section: Discussionmentioning

confidence: 76%

Osteoprogenitor differentiation is not affected by immunomodulatory thalidomide analogs but is promoted by low bortezomib concentration, while both agents suppress osteoclast differentiation

Munemasa

Sakai²,

Kuroda³

et al. 2008

Int J Oncol

View full text Add to dashboard Cite

show abstract

“…afatinib in tumors are reduced by IL-6 in the tumor microenvironment. Indeed, it was reported that IL-6 is detected at higher levels in tumor-associated stroma than in normal bone marrow stroma (42). Furthermore, several studies showed that serum IL-6 levels are elevated in patients with lung cancer than in normal individuals (43,44).…”

Section: Discussionmentioning

confidence: 99%

Activation of IL-6R/JAK1/STAT3 Signaling Induces De Novo Resistance to Irreversible EGFR Inhibitors in Non–Small Cell Lung Cancer with T790M Resistance Mutation

Kim

Kwon

Hong

et al. 2012

Molecular Cancer Therapeutics

179

155

View full text Add to dashboard Cite

The secondary T790M mutation in epidermal growth factor receptor (EGFR) is the major mechanism of acquired resistance to EGFR tyrosine kinase inhibitors (TKI) in non-small cell lung cancer (NSCLC). Although irreversible EGFR TKIs, such as afatinib or dacomitinib, have been introduced to overcome the acquired resistance, they showed a limited efficacy in NSCLC with T790M. Herein, we identified the novel de novo resistance mechanism to irreversible EGFR TKIs in H1975 and PC9-GR cells, which are NSCLC cells with EGFR T790M. Afatinib activated interleukin-6 receptor (IL-6R)/JAK1/STAT3 signaling via autocrine IL-6 secretion in both cells. Inhibition of IL-6R/JAK1/STAT3 signaling pathway increased the sensitivity to afatinib. Cancer cells showed stronger STAT3 activation and enhanced resistance to afatinib in the presence of MRC5 lung fibroblasts. Blockade of IL-6R/JAK1 significantly increased the sensitivity to afatinib through inhibition of afatinib-induced STAT3 activation augmented by the interaction with fibroblasts, suggesting a critical role of paracrine IL-6R/JAK1/STAT3 loop between fibroblasts and cancer cells in the development of drug resistance.

show abstract

“…Several previous studies indicated that BM-derived MSCs from MM patients showed an enhanced production of cytokines and a distinctive gene expression profile, as compared with their normal counterparts. [1][2][3][4] Although osteoblastic function is decreased in advanced MM, regarding whether and at which level the differentiation of MSCs towards osteoblasts is impaired in this disease, the reports are not unanimous. [1][2][3] In the present study, MSCs from both normal subjects (healthy human donors or naive mice) and MM subjects (MM patients or 5T33MM mice) were used.…”

mentioning

confidence: 99%

“…[1][2][3][4] Although osteoblastic function is decreased in advanced MM, regarding whether and at which level the differentiation of MSCs towards osteoblasts is impaired in this disease, the reports are not unanimous. [1][2][3] In the present study, MSCs from both normal subjects (healthy human donors or naive mice) and MM subjects (MM patients or 5T33MM mice) were used. The 5T33MM mice originate from elderly C57Bl/KaLwRij mice that spontaneously developed MM, and the MM model is propagated by intraveneous transfer of diseased BM cells into young syngeneic mice.…”

mentioning

confidence: 99%

“…Chemoimmunotherapies have become a very potent tool to achieve long-lasting remissions in chronic lymphocytic leukemia (CLL) and the addition of rituximab to fludarabine and cyclophosphamide (FCR) was the first treatment shown to increase overall survival. 1 Because alemtuzumab as a single agent is more potent than rituximab in CLL, the rationale for this study was to combine this anti-CD52 antibody with a FC chemotherapy backbone. [2][3][4] Mice were given DAPT or dimethyl sulfoxide (DMSO) intraperitoneally 10 mg/kg daily for 20 days (n ¼ 3/group).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Impaired osteogenic differentiation of mesenchymal stem cells derived from multiple myeloma patients is associated with a blockade in the deactivation of the Notch signaling pathway

Evans

Buckle

et al. 2012

Leukemia

View full text Add to dashboard Cite

Phenotypic and functional characterization of bone marrow mesenchymal stem cells derived from patients with multiple myeloma

Cited by 166 publications

References 30 publications

Osteoprogenitor differentiation is not affected by immunomodulatory thalidomide analogs but is promoted by low bortezomib concentration, while both agents suppress osteoclast differentiation

Osteoprogenitor differentiation is not affected by immunomodulatory thalidomide analogs but is promoted by low bortezomib concentration, while both agents suppress osteoclast differentiation

Activation of IL-6R/JAK1/STAT3 Signaling Induces De Novo Resistance to Irreversible EGFR Inhibitors in Non–Small Cell Lung Cancer with T790M Resistance Mutation

Impaired osteogenic differentiation of mesenchymal stem cells derived from multiple myeloma patients is associated with a blockade in the deactivation of the Notch signaling pathway

Contact Info

Product

Resources

About