Leukemia cells remodel bone marrow stromal cells to generate a protumoral microenvironment via the S100A8-NOX2-ROS signaling pathway
Abstract The bone marrow microenvironment (BMM) plays a crucial role in the pathogenesis and progression of acute myeloid leukemia (AML). AML cells can modify the BMM to establish a more favorable environment for their survival. However, the mechanism about the complex regulatory interplay between t...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-05-01
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| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-01711-x |
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| Summary: | Abstract The bone marrow microenvironment (BMM) plays a crucial role in the pathogenesis and progression of acute myeloid leukemia (AML). AML cells can modify the BMM to establish a more favorable environment for their survival. However, the mechanism about the complex regulatory interplay between the BMM and AML cells remains unclear. In this study, we used proteomic analysis to elucidate the potential mechanisms underlying the interaction between bone marrow stromal cells (BMSCs) and AML cells. We found that the co-culture of AML cells and BMSCs facilitated the proliferation of AML cells, suppressed the proliferation of BMSCs and triggered their senescence. Furthermore, we show the aberrant expression of S100A8 that plays a crucial role in the communication between AML cells and BMSCs. In the co-culture system, overexpression of S100A8 in AML cells activated NOX2 and induced the production of reactive oxygen species (ROS) in the supernatant, thereby suppressing the proliferation of BMSCs and facilitating the senescence of BMSCs. Subsequently, aging BMSCs secreted a variety of cytokines, including IL-6, CXCL5, MIP-1b, etc. as shown by Cytokine Array and qPCR analysis, which had stimulatory effects on the progression of AML. In conclusion, the present study reveals the crucial involvement of the S100A8-NOX2-ROS signaling pathway in mediating communication between AML cells and BMSCs, suggesting that targeting S100A8 may constitute an efficient strategy for AML therapy. |
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| ISSN: | 2045-2322 |