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.
Subject(s)
Adenocarcinoma/blood supply , Adenocarcinoma/metabolism , Neoplasm Proteins/metabolism , Neovascularization, Pathologic/metabolism , Prostatic Neoplasms/blood supply , Prostatic Neoplasms/metabolism , Scavenger Receptors, Class E/metabolism , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Animals , Cell Line, Tumor , HEK293 Cells , Humans , Lipoproteins, LDL/genetics , Lipoproteins, LDL/metabolism , Male , Mice , Mice, Inbred BALB C , Neoplasm Proteins/genetics , Neovascularization, Pathologic/genetics , Neovascularization, Pathologic/pathology , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Scavenger Receptors, Class E/geneticsABSTRACT
In this article, we present a deflection measurement setup for Atomic Force Microscopy (AFM). It is based on a quadrature phase differential interferometer: we measure the optical path difference between a laser beam reflecting above the cantilever tip and a reference beam reflecting on the static base of the sensor. A design with very low environmental susceptibility and another allowing calibrated measurements on a wide spectral range are described. Both enable a very high resolution (down to 2.5×10(-15) m/âHz), illustrated by thermal noise measurements on AFM cantilevers. They present an excellent long-term stability and a constant sensitivity independent of the optical phase of the interferometer. A quick review shows that our precision is equaling or out-performing the best results reported in the literature, but for a much larger deflection range, up to a few µm.
