ArticleCellular oncology (Dordrecht, Netherlands)2021
COX2 confers bone marrow stromal cells to promoting TNFα/TNFR1β-mediated myeloma cell growth and adhesion.
Article in Cellular oncology (Dordrecht, Netherlands), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 8 citations in OpenAlex.
- Bone marrow stromal cells enhance multiple myeloma cells proliferation through regulating LncRNA OVAAL/ENPP1 axis.Open life sciences · 2026Article
- Myeloid-derived suppressor cells in multiple myeloma: mechanistic insights and therapeutic implications.Frontiers in immunology · 2026Review
- High level of circulating cell-free tumor DNA at diagnosis correlates with disease spreading and defines multiple myeloma patients with poor prognosis.Blood cancer journal · 2024Article
- Novel Insights into the Initiation, Evolution, and Progression of Multiple Myeloma by Multi-Omics Investigation.Cancers · 2024Review
- [Latest Findings on the Mechanism of the Interaction Between Multiple Myeloma Cells and Bone Marrow Microenvironment].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2023Review
- Interaction between COX-2 and ER stress is involved in the apoptosis-induced myocardial ischemia/reperfusion injury.American journal of translational research · 2022Article
- Efficacy Evaluation of Inflammatory Mediators in the Treatment of Multiple Myeloma with Daratumumab.Journal of oncology · 2022Article
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Authors and funding
20 authors at 4 institutions in 3 countries.
Funding
Abstract
purposeBone marrow stromal cells (BMSCs) have been implicated in multiple myeloma (MM) progression. However, the underlying mechanisms remain largely elusive. Therefore, we aimed to explore key factors in BMSCs that contribute to MM development.
methodsRNA-sequencing was used to perform gene expression profiling in BMSCs. Enzyme-linked immunosorbent assays (ELISAs) were performed to determine the concentrations of PGE2 and TNFα in sera and conditioned media (CM). Western blotting, qRT-PCR and IHC were used to examine the expression of cyclooxygenase 2 (COX2) in BMSCs and to analyze the regulation of TNFα by COX2. Cell growth and adhesion assays were employed to explore the function of COX2 in vitro. A 5T33MMvt-KaLwRij mouse model was used to study the effects of COX2 inhibition in vivo.
resultsCOX2 was found to be upregulated in MM patient-derived BMSCs and to play a critical role in BMSC-induced MM cell proliferation and adhesion. Administration of PGE2 to CM derived from BMSCs promoted MM cell proliferation and adhesion. Conversely, inhibition of COX2 in BMSCs greatly compromised BMSC-induced MM cell proliferation and adhesion. PCR array-based analysis of inflammatory cytokines indicated that COX2 upregulates the expression of TNFα. Subsequent rescue assays showed that an anti-TNFα monoclonal antibody could antagonize COX2-mediated MM cell proliferation and adhesion. Administration of NS398, a specific COX2 inhibitor, inhibited in vivo tumor growth and improved the survival of 5TMM mice.
conclusionsOur results indicate that COX2 contributes to BMSC-induced MM proliferation and adhesion by increasing the secretion of PGE2 and TNFα. Targeting COX2 in BMSCs may serve as a potential therapeutic approach of treating MM.
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Registered trials
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