Exosomes from BM-MSCs promote acute myeloid leukemia cell proliferation, invasion and chemoresistance via upregulation of S100A4

Experimental Hematology & Oncology

Binglei Zhang¹  Bin Qin¹  Wenli Zhang²  Yongping Song²  Zhiyue Li²  Cheng Cheng²  Tianxin Lyu³  Rongqun Guo⁴  Ding Li⁵  Hui Yang⁶  Yinuo Wang⁶ 

[1] Academy of Medical Sciences, Zhengzhou University, 450052, Zhengzhou, China;Department of Hematology, Affiliated Cancer Hospital of Zhengzhou University, 450008, Zhengzhou, China;Department of Hematology, Affiliated Cancer Hospital of Zhengzhou University, 450008, Zhengzhou, China;Academy of Medical Sciences, Zhengzhou University, 450052, Zhengzhou, China;Department of Hematology, The First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, China;Department of Pharmacy, Affiliated Cancer Hospital of Zhengzhou University, 450008, Zhengzhou, China;Translational Cancer Research Center, Peking University First Hospital, 100034, Beijing, China;

关键词: Acute myeloid leukemia;    Exosome;    Mesenchymal stem cells;    Invasion;    Chemoresistance;   

DOI  :  10.1186/s40164-021-00220-7

来源: Springer

【 摘 要 】

BackgroundBM-MSCs play an important role in cancer development through the release of cytokines or exosomes. Studies have shown that extracellular exosomes derived from BM-MSCs are a key pro-invasive factor. However, how BM-MSC-exos influence AML cell proliferation, invasion and chemoresistance remains poorly understood.MethodsWe isolated exosomes from BM-MSCs and used electron microscopy, particle size separation and western blots to identify the exosomes. The invasion of leukemia cells was observed with a transwell assay. The stemness traits and chemoresistance of the leukemia cells were detected by FCM, colony formation and CCK-8 assays. TCGA database was used to investigate the prognostic relevance of S100A4 and its potential role in AML.ResultsIn this study, we found that BM-MSC-exos increased the metastatic potential, maintained the stemness and contributed to the chemoresistance of leukemia cells. Mechanistically, BM-MSC-exos promoted the proliferation, invasion and chemoresistance of leukemia cells via upregulation of S100A4. Downregulating S100A4 clearly suppressed the proliferation, invasion, and chemoresistance of leukemia cells after treatment with BM-MSC-exos. Bioinformatic analysis with data in TCGA database showed that S100A4 was associated with poor prognosis in AML patients, and functional enrichment revealed its involvement in the processes of cell–cell adhesion and cytokine regulation.ConclusionsS100A4 is vital in the BM-MSC-exo-driven proliferation, invasion and chemoresistance of leukemia cells and may serve as a potential target for leukemia therapy.

【 授权许可】

CC BY