title: Lectin-like oxidized LDL receptor-1 is an enhancer of tumor angiogenesis in human prostate cancer cells.
abstract: Altered expression and function of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) has been associated with several diseases such as endothelial dysfunction, atherosclerosis and obesity. In these pathologies, oxLDL/LOX-1 activates signaling pathways that promote cell proliferation, cell motility and angiogenesis. Recent studies have indicated that olr1 mRNA is over-expressed in stage III and IV of human prostatic adenocarcinomas. However, the function of LOX-1 in prostate cancer angiogenesis remains to be determined. Our aim was to analyze the contribution of oxLDL and LOX-1 to tumor angiogenesis using C4-2 prostate cancer cells. We analyzed the expression of pro-angiogenic molecules and angiogenesis on prostate cancer tumor xenografts, using prostate cancer cell models with overexpression or knockdown of LOX-1 receptor. Our results demonstrate that the activation of LOX-1 using oxLDL increases cell proliferation, and the expression of the pro-angiogenic molecules VEGF, MMP-2, and MMP-9 in a dose-dependent manner. Noticeably, these effects were prevented in the C4-2 prostate cancer model when LOX-1 expression was knocked down. The angiogenic effect of LOX-1 activated with oxLDL was further demonstrated using the aortic ring assay and the xenograft model of tumor growth on chorioallantoic membrane of chicken embryos. Consequently, we propose that LOX-1 activation by oxLDL is an important event that enhances tumor angiogenesis in human prostate cancer cells.
authors.affiliation: Biotechnology and Biopharmaceuticals Laboratory, Department of Pathophysiology, School of Biological Sciences, Universidad de Concepción, Concepción, Chile.
authors.forename: Iván
authors.initials: I
authors.lastname: González-Chavarría
authors.affiliation: Biotechnology and Biopharmaceuticals Laboratory, Department of Pathophysiology, School of Biological Sciences, Universidad de Concepción, Concepción, Chile.
authors.forename: Rita P
authors.initials: RP
authors.lastname: Cerro
authors.affiliation: Biotechnology and Biopharmaceuticals Laboratory, Department of Pathophysiology, School of Biological Sciences, Universidad de Concepción, Concepción, Chile.
authors.forename: Natalie P
authors.initials: NP
authors.lastname: Parra
authors.affiliation: Biotechnology and Biopharmaceuticals Laboratory, Department of Pathophysiology, School of Biological Sciences, Universidad de Concepción, Concepción, Chile.
authors.forename: Felipe A
authors.initials: FA
authors.lastname: Sandoval
authors.affiliation: Department of Clinical Biochemistry and Immunology, School of Pharmacy, Universidad de Concepción, Concepción, Chile.
authors.forename: Felipe A
authors.initials: FA
authors.lastname: Zuñiga
authors.affiliation: Department of Basic Sciences, Faculty of Medicine, Universidad Católica de la Santísima Concepción, Concepción, Chile.
authors.forename: Valeska A
authors.initials: VA
authors.lastname: Omazábal
authors.affiliation: Department of Clinical Biochemistry and Immunology, School of Pharmacy, Universidad de Concepción, Concepción, Chile.
authors.forename: Liliana I
authors.initials: LI
authors.lastname: Lamperti
authors.affiliation: Biotechnology and Biopharmaceuticals Laboratory, Department of Pathophysiology, School of Biological Sciences, Universidad de Concepción, Concepción, Chile.
authors.forename: Silvana P
authors.initials: SP
authors.lastname: Jiménez
authors.affiliation: Biotechnology and Biopharmaceuticals Laboratory, Department of Pathophysiology, School of Biological Sciences, Universidad de Concepción, Concepción, Chile.
authors.forename: Edelmira A
authors.initials: EA
authors.lastname: Fernandez
authors.affiliation: Biotechnology and Biopharmaceuticals Laboratory, Department of Pathophysiology, School of Biological Sciences, Universidad de Concepción, Concepción, Chile.
authors.forename: Nicolas A
authors.initials: NA
authors.lastname: Gutiérrez
authors.affiliation: Biotechnology and Biopharmaceuticals Laboratory, Department of Pathophysiology, School of Biological Sciences, Universidad de Concepción, Concepción, Chile.
authors.forename: Federico S
authors.initials: FS
authors.lastname: Rodriguez
authors.affiliation: Translational Research Unit, School of Medicine, Universidad de Concepción, Concepción, Chile.
authors.forename: Sergio A
authors.initials: SA
authors.lastname: Onate
authors.affiliation: Department of Pharmacology, School of Biological Sciences, Universidad de Concepción, Concepción, Chile.
authors.forename: Oliberto
authors.initials: O
authors.lastname: Sánchez
authors.affiliation: Biotechnology and Biopharmaceuticals Laboratory, Department of Pathophysiology, School of Biological Sciences, Universidad de Concepción, Concepción, Chile.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Vera
authors.affiliation: Biotechnology and Biopharmaceuticals Laboratory, Department of Pathophysiology, School of Biological Sciences, Universidad de Concepción, Concepción, Chile.
authors.forename: Jorge R
authors.initials: JR
authors.lastname: Toledo
mesh_terms: D000230:Adenocarcinoma / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D045744:Cell Line, Tumor; D057809:HEK293 Cells; D006801:Humans; D008077:Lipoproteins, LDL / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051127:Scavenger Receptors, Class E / Q000235:genetics / Q000378:metabolism*
chemical_list: D008077:Lipoproteins, LDL; D009363:Neoplasm Proteins; C495137:OLR1 protein, human; C495138:Olr1 protein, mouse; D051127:Scavenger Receptors, Class E; C099252:oxidized low density lipoprotein