title: From glioblastoma to endothelial cells through extracellular vesicles: messages for angiogenesis.
abstract: Glioblastoma has one of the highest mortality rates among cancers, and it is the most common and malignant form of brain cancer. Among the typical features of glioblastoma tumors, there is an aberrant vascularization: all gliomas are among the most vascularized/angiogenic tumors. In recent years, it has become clear that glioblastoma cells can secrete extracellular vesicles which are spherical and membrane-enclosed particles released, in vitro or in vivo, by both normal and tumor cells; they are involved in the regulation of both physiological and pathological processes; among the latter, cancer is the most widely studied. Extracellular vesicles from tumor cells convey messages to other tumor cells, but also to normal stromal cells in order to create a microenvironment that supports cancer growth and progression and are implicated in drug resistance, escape from immunosurveillance and from apoptosis, as well as in metastasis formation; they are also involved in angiogenesis stimulation, inducing endothelial cells proliferation, and other pro-angiogenic activities. To this aim, the present paper assesses in detail the extracellular vesicles phenomenon in the human glioblastoma cell line U251 and evaluates extracellular vesicles ability to promote the processes required to achieve the formation of new blood vessels in human brain microvascular endothelial cells, highlighting that they stimulate proliferation, motility, and tube formation in a dose-response manner. Moreover, a molecular characterization shows that extracellular vesicles are fully equipped for angiogenesis stimulation in terms of proteolytic enzymes (gelatinases and plasminogen activators), pro-angiogenic growth factors (VEGF and TGFβ), and the promoting-angiogenic CXCR4 chemokine receptor.
authors.affiliation: Department of Life, Health and Environmental Sciences, University of L'Aquila, Via Vetoio-Coppito 2, I-67100, L'Aquila, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Giusti
authors.affiliation: Department of Applied Clinical Sciences and Biotechnologies, University of L'Aquila, Via Vetoio-Coppito 2, I-67100, L'Aquila, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Delle Monache
authors.affiliation: Department of Life, Health and Environmental Sciences, University of L'Aquila, Via Vetoio-Coppito 2, I-67100, L'Aquila, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Di Francesco
authors.affiliation: Department of Applied Clinical Sciences and Biotechnologies, University of L'Aquila, Via Vetoio-Coppito 2, I-67100, L'Aquila, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Sanità
authors.affiliation: Department of Life, Health and Environmental Sciences, University of L'Aquila, Via Vetoio-Coppito 2, I-67100, L'Aquila, Italy.
authors.forename: Sandra
authors.initials: S
authors.lastname: D'Ascenzo
authors.affiliation: Department of Applied Clinical Sciences and Biotechnologies, University of L'Aquila, Via Vetoio-Coppito 2, I-67100, L'Aquila, Italy.
authors.forename: Giovanni Luca
authors.initials: GL
authors.lastname: Gravina
authors.affiliation: Department of Applied Clinical Sciences and Biotechnologies, University of L'Aquila, Via Vetoio-Coppito 2, I-67100, L'Aquila, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Festuccia
authors.affiliation: Department of Life, Health and Environmental Sciences, University of L'Aquila, Via Vetoio-Coppito 2, I-67100, L'Aquila, Italy. vincenza.dolo@univaq.it.
authors.forename: Vincenza
authors.initials: V
authors.lastname: Dolo
mesh_terms: D001808:Blood Vessels / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D055252:Cell-Derived Microparticles / Q000378:metabolism / Q000648:ultrastructure; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000378:metabolism* / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D055354:Exosomes / Q000378:metabolism / Q000648:ultrastructure; D000067128:Extracellular Vesicles / Q000378:metabolism* / Q000648:ultrastructure; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000503:physiopathology; D019718:Receptors, CXCR4 / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D019718:Receptors, CXCR4; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A
keywords: Angiogenesis; CXCR4; Endothelial cells; Extracellular vesicles; Human glioblastoma; U251 cells