Abstract
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.
Highlights
Acute myeloid leukemia (AML) is a clinically heterogeneous hematologic malignancy characterized by an elevated level of differentiation impairment and by the hyperproliferation of nonlymphoid progenitor cells in the boneLyu et al Exp Hematol Oncol (2021) 10:24 from and is maintained by leukemic stem cells (LSCs), which have many similarities to hematopoietic stem cells (HSCs), including self-renewal capacity and multidifferentiation features [7]
We found that Bone marrow mesenchymal stem cells (BM-MSCs)-exos increased the population of LSCs, enhanced the chemoresistance of leukemic cells, and promoted the release of leukemic cells into peripheral blood
BM‐MSC‐exos promoted the metastatic potential of leukemia cells To identify whether BM-MSC-exos could promote the metastasis of leukemia cells, leukemia cells (KASUMI-1, and THP-1) were treated with exosomes derived from conditioned medium of BM-MSCs
Summary
Acute myeloid leukemia (AML) is a clinically heterogeneous hematologic malignancy characterized by an elevated level of differentiation impairment and by the hyperproliferation of nonlymphoid progenitor cells in the boneLyu et al Exp Hematol Oncol (2021) 10:24 from and is maintained by leukemic stem cells (LSCs), which have many similarities to hematopoietic stem cells (HSCs), including self-renewal capacity and multidifferentiation features [7]. An increasing number of studies have shown that stromal cells, working as tumor microenvironment components, play a vital role in tumor cell proliferation and drug resistance [10]. Bone marrow mesenchymal stem cells (BM-MSCs) are important components of the bone marrow microenvironment, and their interaction with tumor cells can promote tumor formation and progression [11]. MSCs physically contact with adjacent tumor cells and can secrete cytokines. Those cytokines can trigger intercellular signaling, which directly affects the dynamics and fate of tumor cells [12]. 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. How BM-MSC-exos influence AML cell proliferation, invasion and chemoresistance remains poorly understood
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
