Leukemia-derived exosomes induced IL-8 production in bone marrow stromal cells to protect the leukemia cells against chemotherapy

Abstract

AimsThe interplay between bone marrow stromal cells (BMSCs) and acute myeloid leukemia (AML) cells plays a critical role in AML drug resistance by secreting growth factors, cytokines, and extracellular vesicles. As kind of extracellular vesicles, exosomes consist of proteins and RNAs and regulate communication among cells. Main methodsThe BMSCs, HS5 cells, and AML cells were co-cultivated with transwell membranes, and treated with different doses of AML chemotherapy drug, etoposide. Key findingsFindings of our research proved that co-cultivation of BMSCs with AML cells defended AML against cell death triggered via etoposide, without having an impact on cell growth. An increase in the expression of the 70 kDa heat shock proteins (HSP70) as well as lysosomal associated membrane protein 3 (CD63) was observed in the exosomes from BMSC and AML, co-cultivated in conditioned media. Exosome repression in BMSC and AML co-cultivating system rebuilt the sensitivity of the KG1A cells to apoptosis triggered via etoposide, indicating that exosome modulated drug resistance in AML. Our study proved that exosomes arising from KG1A cells could propel BMSCs to generate IL-8, which could regulate the effect of etoposide treatment. Furthermore, IL-8 inhibition by its antibody increased the sensitivity of AML cells to cell death triggered via etoposide. SignificanceOur results suggested that exosomes secreted by AML cells is an essential communicator for the interaction of BMSCs and AML, which can protect AML cells from chemotherapy drug induced apoptosis.