Exosomes released by K562 chronic myeloid leukemia cells promote angiogenesis in a src-dependent fashion
Marco Mineo,Marco Mineo,Susan H. Garfield,Simona Taverna,A. Flugy,Giacomo De Leo,Riccardo Alessandro,Elise C. Kohn +7 more
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The inhibitory effect of dasatinib on exosome production and vascular differentiation and signaling reveals a key role for Src in both the leukemia and its microenvironment.Abstract:
Exosomes, microvesicles of endocytic origin released by normal and tumor cells, play an important role in cell-to-cell communication. Angiogenesis has been shown to regulate progression of chronic myeloid leukemia (CML). The mechanism through which this happens has not been elucidated. We isolated and characterized exosomes from K562 CML cells and evaluated their effects on human umbilical endothelial cells (HUVECs). Fluorescent-labeled exosomes were internalized by HUVECs during tubular differentiation on Matrigel. Exosome localization was perinuclear early in differentiation, moving peripherally in cells undergoing elongation and connection. Exosomes move within and between nanotubular structures connecting the remodeling endothelial cells. They stimulated angiotube formation over a serum/growth factor-limited medium control, doubling total cumulative tube length (P = 0.003). Treatment of K562 cells with two clinically active tyrosine kinase inhibitors, imatinib and dasatinib, reduced their total exosome release (P < 0.009); equivalent concentrations of drug-treated exosomes induced a similar extent of tubular differentiation. However, dasatinib treatment of HUVECs markedly inhibited HUVEC response to drug control CML exosomes (P < 0.002). In an in vivo mouse Matrigel plug model angiogenesis was induced by K562 exosomes and abrogated by oral dasatinib treatment (P < 0.01). K562 exosomes induced dasatinib-sensitive Src phosphorylation and activation of downstream Src pathway proteins in HUVECs. Imatinib was minimally active against exosome stimulation of HUVEC cell differentiation and signaling. Thus, CML cell-derived exosomes induce angiogenic activity in HUVEC cells. The inhibitory effect of dasatinib on exosome production and vascular differentiation and signaling reveals a key role for Src in both the leukemia and its microenvironment.read more
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Engineering hybrid exosomes by membrane fusion with liposomes.
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Human Umbilical Cord Mesenchymal Stem Cell Exosomes Enhance Angiogenesis Through the Wnt4/β-Catenin Pathway
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References
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Journal ArticleDOI
Exosomes: composition, biogenesis and function
TL;DR: The physical properties that define exosomes as a specific population of secreted vesicles are described, their biological effects, particularly on the immune system, are summarized, and the potential roles that secretedvesicles could have as intercellular messengers are discussed.
Journal ArticleDOI
Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers
Johan Skog,T. Wurdinger,van Rijn S,Dimphna H. Meijer,Gainche L,Miguel Sena-Esteves,William T. Curry,Bob S. Carter,Anna M. Krichevsky,Xandra O. Breakefield +9 more
TL;DR: Tumour-derived microvesicles may provide diagnostic information and aid in therapeutic decisions for cancer patients through a blood test by incorporating an mRNA for a reporter protein into them, and it is demonstrated that messages delivered by microvesicle are translated by recipient cells.
Journal ArticleDOI
Letter: A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining.
TL;DR: An unsuspected abnormality in all cells from the nine patients with chronic myelogenous leukaemia has been detected with quinacrine fluorescence and various Giemsa staining techniques, suggesting that there may be a hitherto undetected translocation between the long arm of 22 and thelong arm of 9, producing the 9q+ chromosome.
Journal ArticleDOI
Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells.
Brian J. Druker,Shu Tamura,Elisabeth Buchdunger,Sayuri Ohno,Gerald M. Segal,Shane Fanning,Jürg Zimmermann,Nicholas B. Lydon +7 more
TL;DR: A compound, designed to inhibit the Abl protein tyrosine kinase, was evaluated for its effects on cells containing the Bcr–Abl fusion protein and it was found that this compound may be useful in the treatment of bcr–abl–positive leukemias.
Journal ArticleDOI
Membrane vesicles as conveyors of immune responses
TL;DR: The role of membrane vesicles, in particular exosomes, in the communication between immune cells, and between tumour and immune cells is focused on.
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