6533b862fe1ef96bd12c6313

RESEARCH PRODUCT

Exosome-mediated crosstalk between chronic myelogenous leukemia cells and human bone marrow stromal cells triggers an Interleukin 8-dependent survival of leukemia cells

Laura SaievaRaimondo StefaniaRiccardo AlessandroA. FlugyChiara CorradoGiacomo De Leo

subject

MaleCancer ResearchChemokineStromal cellCell SurvivalMice SCIDExosomesChronic myelogenous leukemia Bone marrow stromal cells Tumour microenvironment Exosomes Interleukin 8ExosomeMiceCell MovementMice Inbred NODSettore BIO/13 - Biologia ApplicataCell Line TumorLeukemia Myelogenous Chronic BCR-ABL Positivehemic and lymphatic diseasesParacrine CommunicationCell AdhesionTumor MicroenvironmentmedicineAnimalsHumansCXC chemokine receptorsStem Cell NichebiologyInterleukin-8Mesenchymal Stem Cellsmedicine.diseaseUp-RegulationLeukemiaPhenotypemedicine.anatomical_structureOncologyCancer cellImmunologyCancer researchbiology.proteinHeterograftsBone marrowSignal TransductionChronic myelogenous leukemia

description

Chronic myelogenous leukemia (CML) is a myeloproliferative disorder characterized by the Bcr-Abl oncoprotein with constitutive tyrosine kinase activity. Exosomes are nanovesicles released by cancer cells that are involved in cell-to-cell communication thus potentially affecting cancer progression. It is well known that bone marrow stromal microenvironment contributes to disease progression through the establishment of a bi-directional crosstalk with cancer cells. Our hypothesis is that exosomes could have a functional role in this crosstalk. Interleukin-8 (IL 8) is a proinflammatory chemokine that activates multiple signalling pathways downstream of two receptors (CXCR1 and CXCR2). We demonstrated that exosomes released from CML cells stimulate bone marrow stromal cells to produce IL 8 that, in turn, is able to modulate both in vitro and in vivo the leukemia cell malignant phenotype.

https://doi.org/10.1016/j.canlet.2014.03.009