Abstract | BACKGROUND: BM-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. METHODS: We 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. RESULTS: In 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. CONCLUSIONS: S100A4 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.
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Authors | Tianxin Lyu, Yinuo Wang, Ding Li, Hui Yang, Bin Qin, Wenli Zhang, Zhiyue Li, Cheng Cheng, Binglei Zhang, Rongqun Guo, Yongping Song |
Journal | Experimental hematology & oncology
(Exp Hematol Oncol)
Vol. 10
Issue 1
Pg. 24
(Mar 31 2021)
ISSN: 2162-3619 [Print] England |
PMID | 33789743
(Publication Type: Journal Article)
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