BACKGROUND: Tumour-derived microvesicles (TMVs) may interact with cells of the immune system. Our previous observations indicated that TMVs modulate production of cytokines and reactive oxygen species (ROS) by monocytes. This study was designed to determine the role of TMVs in stimulation of chemokine production by human monocytes. MATERIALS AND METHODS: Chemokines at the mRNA and protein level were detected by real-time PCR and by Western blot, respecively. Chemokine release and chemotaxis of blood leukocytes were analysed by flow cytometry. Matrigel assay was used to determine angiogenesis in a NOD-SCID mice model. RESULTS: TMVs induced secretion of interleukin-8 (CXCL8), monocyte chemoattractant protein-1 (CCL2), macrophage inflammatory protein-1α (CCL3) and MIP-1β (CCL4), and regulated on activation normal T-cells expressed and secreted (CCL5) chemokines and accumulation of their mRNA in monocytes. Moreover, TMVs enhanced angiogenesis in NOD-SCID mice by delivering chemokines and via stimulation of monocytes. In addition, TMVs may be storage for chemokines thus inducing chemotaxis of blood leukocytes. CONCLUSION: These results further support the role of TMVs in modulation of monocyte biological activity.
BACKGROUND: Tumour-derived microvesicles (TMVs) may interact with cells of the immune system. Our previous observations indicated that TMVs modulate production of cytokines and reactive oxygen species (ROS) by monocytes. This study was designed to determine the role of TMVs in stimulation of chemokine production by human monocytes. MATERIALS AND METHODS: Chemokines at the mRNA and protein level were detected by real-time PCR and by Western blot, respecively. Chemokine release and chemotaxis of blood leukocytes were analysed by flow cytometry. Matrigel assay was used to determine angiogenesis in a NOD-SCIDmice model. RESULTS:TMVs induced secretion of interleukin-8 (CXCL8), monocyte chemoattractant protein-1 (CCL2), macrophage inflammatory protein-1α (CCL3) and MIP-1β (CCL4), and regulated on activation normal T-cells expressed and secreted (CCL5) chemokines and accumulation of their mRNA in monocytes. Moreover, TMVs enhanced angiogenesis in NOD-SCIDmice by delivering chemokines and via stimulation of monocytes. In addition, TMVs may be storage for chemokines thus inducing chemotaxis of blood leukocytes. CONCLUSION: These results further support the role of TMVs in modulation of monocyte biological activity.
Authors: María Yáñez-Mó; Pia R-M Siljander; Zoraida Andreu; Apolonija Bedina Zavec; Francesc E Borràs; Edit I Buzas; Krisztina Buzas; Enriqueta Casal; Francesco Cappello; Joana Carvalho; Eva Colás; Anabela Cordeiro-da Silva; Stefano Fais; Juan M Falcon-Perez; Irene M Ghobrial; Bernd Giebel; Mario Gimona; Michael Graner; Ihsan Gursel; Mayda Gursel; Niels H H Heegaard; An Hendrix; Peter Kierulf; Katsutoshi Kokubun; Maja Kosanovic; Veronika Kralj-Iglic; Eva-Maria Krämer-Albers; Saara Laitinen; Cecilia Lässer; Thomas Lener; Erzsébet Ligeti; Aija Linē; Georg Lipps; Alicia Llorente; Jan Lötvall; Mateja Manček-Keber; Antonio Marcilla; Maria Mittelbrunn; Irina Nazarenko; Esther N M Nolte-'t Hoen; Tuula A Nyman; Lorraine O'Driscoll; Mireia Olivan; Carla Oliveira; Éva Pállinger; Hernando A Del Portillo; Jaume Reventós; Marina Rigau; Eva Rohde; Marei Sammar; Francisco Sánchez-Madrid; N Santarém; Katharina Schallmoser; Marie Stampe Ostenfeld; Willem Stoorvogel; Roman Stukelj; Susanne G Van der Grein; M Helena Vasconcelos; Marca H M Wauben; Olivier De Wever Journal: J Extracell Vesicles Date: 2015-05-14
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