Lectin-Like Oxidized LDL Receptor-1 Is an Enhancer of Tumor Angiogenesis in Human Prostate Cancer Cells
Date
2014Author
Cerro, Rita P.
Parra, Natalie P.
González-Chavarría, Iván
Sandoval, Felipe A.
Zuñiga, Felipe Andrés
Ormazábal, Valeska
Lamperti, Liliana I.
Jiménez, Silvana P.
Fernández, Edelmira A.
Gutiérrez, Nicolas A.
Rodríguez, Federico S.
Onate, Sergio A.
Sánchez, Oliberto
Vera, Juan C.
Toledo, Jorge R.
Description
Artículo de publicación ISIMetadata
Show full item recordAbstract
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.