Related Experiment Video
Updated: Nov 6, 2025
Proliferation and Differentiation of Murine Myeloid Precursor 32D/G-CSF-R Cells
Published on: February 21, 2018
Bone marrow cells are differentiated into MDSCs by BCC-Ex through down-regulating the expression of CXCR4 and
Quan-Wen Liu1, Yong Chen1, Jing-Yuan Li2
1The National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang University, Nanchang, China.
Abstract:
Studies showed that the increase of myeloid-derived suppressor cells (MDSCs) in tumour microenvironment is closely related to the resistant treatment and poor prognosis of metastatic breast cancer. However, the effect of tumour-derived exosomes on MDSCs and its mechanism are not clear. Here, we reported that breast cancer cells (4T1)-secreted exosomes (BCC-Ex) were able to differentiate bone marrow cells into MDSCs and significantly inhibited the proliferation of T lymphocytes to provide an immunosuppressive microenvironment for cancer cells in vivo and in vitro. The number of MDSCs in bone marrow and spleen of 4T1 tumour-bearing mice and BCC-Ex infused mice was significantly higher than that of normal mice, whereas the number of T lymphocytes in spleen was significantly decreased. In addition, BCC-Ex markedly promoted the differentiation of MDSCs from bone marrow cells or bone marrow cells derived macrophages, seen as the increased expressions of MDSCs-related functional proteins Arginase-1 (Arg-1) and inducible nitric oxide synthase (iNOS). Furthermore, BCC-Ex significantly down-regulated the expressions of chemokine receptor CXCR4 and markedly up-regulated the levels of inflammatory cytokines IL-6 and IL-10 in bone marrow cells and macrophages and remarkably inhibited the division and proliferation of T cells. Importantly, CXCR4 agonist, CXCL12, could reverse the function of BCC-Ex, indicating that BCC-Ex-induced MDSCs might be dependent on the down-regulation of CXCR4. Western blot showed that BCC-Ex significantly promoted the phosphorylation of STAT3 in bone marrow cells, resulting in the inhibitions of the proliferation and apoptosis of bone marrow cells, and the aggravation of the differentiation of bone marrow cells into MDSCs.
Insights
Breast cancer cells release exosomes that promote myeloid-derived suppressor cells (MDSCs) and suppress T cells, creating an immunosuppressive tumor microenvironment. This exosome-mediated immune suppression is linked to poor metastatic breast cancer prognosis.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- Increased myeloid-derived suppressor cells (MDSCs) correlate with treatment resistance and poor prognosis in metastatic breast cancer.
- The precise mechanisms by which tumor-derived exosomes influence MDSCs remain unclear.
Purpose of the Study:
- To investigate the effect of breast cancer cell-secreted exosomes (BCC-Ex) on MDSCs.
- To elucidate the underlying mechanisms of exosome-mediated immune suppression in breast cancer.
Main Methods:
- In vitro and in vivo experiments using 4T1 breast cancer cells and their secreted exosomes (BCC-Ex).
- Analysis of MDSC differentiation, T lymphocyte proliferation, and expression of key proteins (Arg-1, iNOS, CXCR4, STAT3) and cytokines (IL-6, IL-10).
- Assessment of the role of CXCR4 signaling using its agonist CXCL12.
Main Results:
- BCC-Ex promoted bone marrow cell differentiation into MDSCs and suppressed T lymphocyte proliferation in vitro and in vivo.
- BCC-Ex increased MDSC markers (Arg-1, iNOS) and inflammatory cytokines (IL-6, IL-10) while down-regulating CXCR4.
- STAT3 phosphorylation was enhanced by BCC-Ex, contributing to MDSC differentiation and reduced apoptosis.
- CXCL12 treatment reversed BCC-Ex-induced MDSC differentiation, suggesting CXCR4 dependence.
Conclusions:
- Breast cancer cell-secreted exosomes induce MDSCs and create an immunosuppressive tumor microenvironment.
- The mechanism involves down-regulation of CXCR4 and activation of STAT3 signaling.
- These findings highlight exosome-mediated immune suppression as a potential therapeutic target in metastatic breast cancer.
More Related Videos
05:10Purification, Expansion, and Flow Cytometry-Based Phenotyping of Mouse Derived Bone Marrow Mesenchymal Stem Cells
Published on: July 11, 2025
09:20Differentiation of Monocytes into Phenotypically Distinct Macrophages After Treatment with Human Cord Blood Stem Cell CB-SC-Derived Exosomes
Published on: November 12, 2020
Related Concept Videos
01:15Differentiation of Common Myeloid Progenitor Cells
01:01Regulation of Hematopoietic Stem Cells
01:19Mesenchymal Stem Cells