Lectin-like oxidized LDL receptor-1 is an enhancer of tumor angiogenesis in human prostate cancer cells

PLoS One. 2014 Aug 29;9(8):e106219. doi: 10.1371/journal.pone.0106219. eCollection 2014.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / blood supply*
  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Animals
  • Cell Line, Tumor
  • HEK293 Cells
  • Humans
  • Lipoproteins, LDL / genetics
  • Lipoproteins, LDL / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism*
  • Neovascularization, Pathologic / pathology
  • Prostatic Neoplasms / blood supply*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • Scavenger Receptors, Class E / genetics
  • Scavenger Receptors, Class E / metabolism*

Substances

  • Lipoproteins, LDL
  • Neoplasm Proteins
  • OLR1 protein, human
  • Olr1 protein, mouse
  • Scavenger Receptors, Class E
  • oxidized low density lipoprotein

Grants and funding

This research was supported by Fondecyt Grant 1121159, Conicyt, Chile. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.