title: Curcumin modulates chronic myelogenous leukemia exosomes composition and affects angiogenic phenotype via exosomal miR-21.
abstract: Tumor derived exosomes are vesicles which contain proteins and microRNAs that mediate cell-cell communication and are involved in angiogenesis and tumor progression. Curcumin derived from the plant Curcuma longa, shows anticancer effects. Exosomes released by CML cells treated with Curcumin contain a high amount of miR-21 that is shuttled into the endothelial cells in a biologically active form. The treatment of HUVECs with CML Curcu-exosomes reduced RhoB expression and negatively modulated endothelial cells motility. We showed that the addition of CML control exosomes to HUVECs caused an increase in IL8 and VCAM1 levels, but Curcu-exosomes reversed these effects thus attenuating their angiogenic properties. This antiangiogenic effect was confirmed with in vitro and in vivo vascular network formation assays. SWATH analysis of the proteomic profile of Curcu-exosomes revealed that Curcumin treatment deeply changes their molecular properties, in particular, Curcumin induces a release of exosomes depleted in pro-angiogenic proteins and enriched in proteins endowed with anti-angiogenic activity. Among the proteins differential expressed we focused on MARCKS, since it was the most modulated protein and a target of miR-21. Taken together our data indicated that also Curcumin attenuates the exosome's ability to promote the angiogenic phenotype and to modulate the endothelial barrier organization.
authors.affiliation: Dipartimento di Biopatologia e Metodologie Biomediche, Sezione di Biologia e Genetica, Università di Palermo, Palermo, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Taverna
authors.affiliation: Dipartimento di Biopatologia e Metodologie Biomediche, Sezione di Biologia e Genetica, Università di Palermo, Palermo, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Fontana
authors.affiliation: Dipartimento di Biopatologia e Metodologie Biomediche, Sezione di Biologia e Genetica, Università di Palermo, Palermo, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Monteleone
authors.affiliation: Dipartimento di Biopatologia e Metodologie Biomediche, Sezione di Biologia e Genetica, Università di Palermo, Palermo, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Pucci
authors.affiliation: Dipartimento di Biopatologia e Metodologie Biomediche, Sezione di Biologia e Genetica, Università di Palermo, Palermo, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Saieva
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche, Università di Palermo, Palermo, Italy.
authors.forename: Viviana
authors.initials: V
authors.lastname: De Caro
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche, Università di Palermo, Palermo, Italy.
authors.forename: Valeria Giunta
authors.initials: VG
authors.lastname: Cardinale
authors.affiliation: Dipartimento di Biopatologia e Metodologie Biomediche, Sezione di Biologia e Genetica, Università di Palermo, Palermo, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Giallombardo
authors.affiliation: Dipartimento di Biopatologia e Metodologie Biomediche, Sezione di Biologia e Genetica, Università di Palermo, Palermo, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Vicario
authors.affiliation: Phase I-Early Clinical Trials Unit, Oncology Department, Antwerp University Hospital (UZA) and Center for Oncological Research (CORE) Antwerp University, Edegem, Antwerp, Belgium.
authors.forename: Christian
authors.initials: C
authors.lastname: Rolfo
authors.affiliation: Dipartimento di Biopatologia e Metodologie Biomediche, Sezione di Biologia e Genetica, Università di Palermo, Palermo, Italy.
authors.forename: Giacomo De
authors.initials: GD
authors.lastname: Leo
authors.affiliation: Dipartimento di Biopatologia e Metodologie Biomediche, Sezione di Biologia e Genetica, Università di Palermo, Palermo, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Alessandro
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003474:Curcumin / Q000494:pharmacology*; D055354:Exosomes / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D000076250:Myristoylated Alanine-Rich C Kinase Substrate / Q000235:genetics / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000235:genetics; D018919:Neovascularization, Physiologic / Q000235:genetics; D020543:Proteome / Q000235:genetics / Q000378:metabolism; D040901:Proteomics / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; C000619710:MARCKS protein, human; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D020543:Proteome; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D003474:Curcumin
keywords: CML; curcumin; exosomes; miR-21