title: Role of exosomes released by chronic myelogenous leukemia cells in angiogenesis.
abstract: Our study is designed to assess if exosomes released from chronic myelogenous leukemia (CML) cells may modulate angiogenesis. We have isolated and characterized the exosomes generated from LAMA84 CML cells and demonstrated that addition of exosomes to human vascular endothelial cells (HUVEC) induces an increase of both ICAM-1 and VCAM-1 cell adhesion molecules and interleukin-8 expression. The stimulation of cell-cell adhesion molecules was paralleled by a dose-dependent increase of adhesion of CML cells to a HUVEC monolayer. We further showed that the treatment with exosomes from CML cells caused an increase in endothelial cell motility accompanied by a loss of VE-cadherin and β-catenin from the endothelial cell surface. Functional characterization of exosomes isolated from CML patients confirmed the data obtained with exosomes derived from CML cell line. CML exosomes caused reorganization into tubes of HUVEC cells cultured on Matrigel. When added to Matrigel plugs in vivo, exosomes induced ingrowth of murine endothelial cells and vascularization of the Matrigel plugs. Our results suggest for the first time that exosomes released from CML cells directly affect endothelial cells modulating the process of neovascularization.
authors.affiliation: Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, Sezione di Biologia e Genetica, Università di Palermo, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Taverna
authors.forename: Anna
authors.initials: A
authors.lastname: Flugy
authors.forename: Laura
authors.initials: L
authors.lastname: Saieva
authors.forename: Elise C
authors.initials: EC
authors.lastname: Kohn
authors.forename: Alessandra
authors.initials: A
authors.lastname: Santoro
authors.forename: Serena
authors.initials: S
authors.lastname: Meraviglia
authors.forename: Giacomo
authors.initials: G
authors.lastname: De Leo
authors.forename: Riccardo
authors.initials: R
authors.lastname: Alessandro
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D003094:Collagen / Q000378:metabolism; D004338:Drug Combinations; D055354:Exosomes / Q000378:metabolism* / Q000648:ultrastructure; D005786:Gene Expression Regulation; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism; D059016:Tumor Microenvironment; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D003094:Collagen; D004338:Drug Combinations; D018799:Intercellular Adhesion Molecule-1; D016209:Interleukin-8; D007797:Laminin; D011509:Proteoglycans; D019010:Vascular Cell Adhesion Molecule-1; D051176:beta Catenin; D000099152:Cadherin 5; C059485:matrigel