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Updated: Jan 26, 2026
An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells
Published on: July 15, 2015
Myeloid-derived suppressor cells endow stem-like qualities to multiple myeloma cells by inducing piRNA-823 expression
Lisha Ai1, Shidai Mu1, Chunyan Sun1
1Institute of Hematology, Union Hospital,Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Background:
Myeloid-derived suppressor cells (MDSCs) and cancer stem cells (CSCs) are two important cellular components in the tumor microenvironment, which may modify the cancer phenotype and affect patient survival. However, the crosstalk between MDSCs and multiple myeloma stem cells (MMSCs) are relatively poorly understood.
Methods:
The frequencies of granulocytic-MDSCs (G-MDSCs) in MM patients were detected by flow cytometry and their association with the disease stage and patient survival were analyzed. RT-PCR, flow cytometry, western blot and sphere formation assays were performed to investigate the effects of G-MDSCs, piRNA-823 and DNA methylation on the maintenance of stemness in MM. Then a subcutaneous tumor mouse model was constructed to analyze tumor growth and angiogenesis after G-MDSCs induction and/or piRNA-823 knockdown in MM cells.
Results:
Our clinical dataset validated the association between high G-MDSCs levels and poor overall survival in MM patients. In addition, for the first time we showed that G-MDSCs enhanced the side population, sphere formation and expression of CSCs core genes in MM cells. Moreover, the mechanism study showed that G-MDSCs triggered piRNA-823 expression, which then promoted DNA methylation and increased the tumorigenic potential of MM cells. Furthermore, silencing of piRNA-823 in MM cells reduced the stemness of MMSCs maintained by G-MDSCs, resulting in decreased tumor burden and angiogenesis in vivo.
Conclusion:
Altogether, these data established a cellular, molecular, and clinical network among G-MDSCs, piRNA-823, DNA methylation and CSCs core genes, suggesting a new anti-cancer strategy targeting both G-MDSCs and CSCs in MM microenvironment.
Insights
High levels of granulocytic-myeloid-derived suppressor cells (G-MDSCs) correlate with poor survival in multiple myeloma (MM) patients. These cells promote cancer stem cell (CSC) traits via piRNA-823 and DNA methylation, suggesting a novel therapeutic target.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Myeloid-derived suppressor cells (MDSCs) and cancer stem cells (CSCs) are key factors in the tumor microenvironment influencing cancer progression.
- The interaction between MDSCs and multiple myeloma stem cells (MMSCs) remains poorly understood.
Purpose of the Study:
- To investigate the association between granulocytic-MDSCs (G-MDSCs) and patient survival in multiple myeloma (MM).
- To elucidate the underlying mechanisms by which G-MDSCs influence MMSC stemness and tumor growth.
- To explore a potential therapeutic strategy targeting G-MDSCs and CSCs in MM.
Main Methods:
- Flow cytometry to quantify G-MDSC frequencies in MM patients.
- RT-PCR, western blot, and sphere formation assays to assess G-MDSC effects on MMSC stemness.
- In vivo mouse models to evaluate tumor growth and angiogenesis following G-MDSC induction or piRNA-823 knockdown.
Main Results:
- Elevated G-MDSC levels are linked to reduced overall survival in MM patients.
- G-MDSCs enhance MMSC stemness, indicated by increased side population, sphere formation, and CSC core gene expression.
- G-MDSCs upregulate piRNA-823, promoting DNA methylation and increasing MM cell tumorigenicity.
- Silencing piRNA-823 diminishes G-MDSC-mediated stemness, reducing tumor burden and angiogenesis in vivo.
Conclusions:
- A significant network exists between G-MDSCs, piRNA-823, DNA methylation, and CSCs in MM.
- Targeting G-MDSCs and CSCs presents a promising anti-cancer strategy for multiple myeloma.
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