title: Role of plasma membrane caveolae/lipid rafts in VEGF-induced redox signaling in human leukemia cells.
abstract: Caveolae/lipid rafts are membrane-rich cholesterol domains endowed with several functions in signal transduction and caveolin-1 (Cav-1) has been reported to be implicated in regulating multiple cancer-associated processes, ranging from tumor growth to multidrug resistance and angiogenesis. Vascular endothelial growth factor receptor-2 (VEGFR-2) and Cav-1 are frequently colocalized, suggesting an important role played by this interaction on cancer cell survival and proliferation. Thus, our attention was directed to a leukemia cell line (B1647) that constitutively produces VEGF and expresses the tyrosine-kinase receptor VEGFR-2. We investigated the presence of VEGFR-2 in caveolae/lipid rafts, focusing on the correlation between reactive oxygen species (ROS) production and glucose transport modulation induced by VEGF, peculiar features of tumor proliferation. In order to better understand the involvement of VEGF/VEGFR-2 in the redox signal transduction, we evaluated the effect of different compounds able to inhibit VEGF interaction with its receptor by different mechanisms, corroborating the obtained results by immunoprecipitation and fluorescence techniques. Results here reported showed that, in B1647 leukemia cells, VEGFR-2 is present in caveolae through association with Cav-1, demonstrating that caveolae/lipid rafts act as platforms for negative modulation of VEGF redox signal transduction cascades leading to glucose uptake and cell proliferation, suggesting therefore novel potential targets.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Ferrara, Via Fossato di Mortara 66, 44121 Ferrara, Italy.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Caliceti
authors.affiliation: Department of Pharmacy and Biotechnology, Alma Mater Studiorum-University of Bologna, Via Irnerio 48, 40126 Bologna, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Zambonin
authors.affiliation: Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, C.so Augusto 237, 47921 Rimini, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Rizzo
authors.affiliation: Department of Pharmacy and Biotechnology, Alma Mater Studiorum-University of Bologna, Via Irnerio 48, 40126 Bologna, Italy.
authors.forename: Diana
authors.initials: D
authors.lastname: Fiorentini
authors.affiliation: Department of Pharmacy and Biotechnology, Alma Mater Studiorum-University of Bologna, Via Irnerio 48, 40126 Bologna, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Vieceli Dalla Sega
authors.affiliation: Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, C.so Augusto 237, 47921 Rimini, Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Hrelia
authors.affiliation: Department of Pharmacy and Biotechnology, Alma Mater Studiorum-University of Bologna, Via Irnerio 48, 40126 Bologna, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Prata
mesh_terms: D021941:Caveolae / Q000378:metabolism; D051242:Caveolin 1 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D007938:Leukemia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D021962:Membrane Microdomains / Q000378:metabolism*; D009389:Neovascularization, Pathologic; D010084:Oxidation-Reduction; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D051242:Caveolin 1; D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2
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