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.

Lectin-like oxidized low-density lipoprotein receptor-1 facilitates metastasis of gastric cancer through driving epithelial-mesenchymal transition and PI3K/Akt/GSK3β activation

“…Taken together, the results indicate that LOX-1 promotes the invasion and migration of GC cells via PI3K/Akt/GSK3β-mediated EMT. Additionally, by binding to ox-LDL, LOX-1 could increase the expression of several proangiogenic factors such as vascular endothelial growth factor and matrix metalloprotease343536, which could contribute to tumor growth, invasion and metastasis3738. These findings indicate another mechanism that LOX-1 may also enhance tumor angiogenesis to facilitate cancer metastasis.…”

C-Type Lectin-Like Receptors: Head or Tail in Cell Death Immunity

“…Thus, a high expression of LOX-1 is correlated with a worse prognosis in patients suffering from gastric (69), colorectal (70), or prostate (71) cancer. Functionally, the triggering of LOX-1 by oxLDL was shown to induce TNF-α expression, tumor angiogenesis and tumor cell trans-endothelial migration and metastasis in prostate or breast cancers (71,72). Interestingly, a high expression of LOX-1 was reported on polymorphonuclear myeloid-derived suppressor cells from peripheral blood and tumor of cancer patients (up to 5-50%), whereas its expression is almost undetectable on blood neutrophils from healthy donors (73).…”

LOX‐1: Its cytotopographical variance and disease stress

“…Increased expression of LOX‐1 has been seen in human prostate adenocarcinomas at stages III and IV which require new vascularization and angiogenesis for local invasion . It has also been suggested that LOX‐1 is an essential regulator in prostate cancer cells, with the ability to enhance tumor angiogenesis toward malignancy and metastasis in obese patients . In a recent work, it was suggested that LOX‐1 is a novel biomarker and molecular target for colorectal cancer.…”