Lysophosphatidic acid enhances vascular endothelial growth factor-C expression in human prostate cancer PC-3 cells
Journal
PLoS ONE
Journal Volume
7
Journal Issue
7
Date Issued
2012
Author(s)
Abstract
Clinical evidence suggests that lymphangiogenesis and lymphatic metastasis are important processes during the progression of prostate cancer. Vascular endothelial growth factor (VEGF)-C was shown to be a key regulator in these processes. Our previous studies demonstrated that lysophosphatidic acid (LPA), a low-molecular-weight lipid growth factor, enhances VEGF-C expression in human endothelial cells. We previously demonstrated that the LPA receptor plays an important role in lymphatic development in zebrafish embryos. However, the effects of LPA on VEGF-C expression in prostate cancer are not known. Herein, we demonstrate that LPA up-regulated VEGF-C expression in three different human prostate cancer cell lines. In PC-3 human prostate cancer cells, the enhancing effects of LPA were mediated through both LPA1 and LPA3. In addition, reactive oxygen species (ROS) production and lens epithelium-derived growth factor (LEDGF) expression were involved in LPA1/3-dependent VEGF-C expression. Furthermore, autotaxin (ATX), an enzyme responsible for LPA synthesis, also participates in regulating VEGF-C expression. By interrupting LPA1/3 of PC-3, conditioned medium (CM) -induced human umbilical vein endothelial cell (HUVEC) lymphatic markers expression was also blocked. In summary, we found that LPA enhances VEGF-C expression through activating LPA1/3-, ROS-, and LEDGF-dependent pathways. These novel findings could potentially shed light on developing new strategies for preventing lymphatic metastasis of prostate cancer. ? 2012 Lin et al.
SDGs
Other Subjects
autotaxin; biological marker; lens epithelium derived growth factor; lysophosphatidic acid; lysophosphatidic acid receptor; lysophosphatidic acid receptor 1; lysophosphatidic acid receptor 3; messenger RNA; reactive oxygen metabolite; unclassified drug; vasculotropin C; article; autotaxin gene; cancer cell culture; controlled study; enzyme mechanism; enzyme regulation; gene expression regulation; gene function; gene silencing; human; human cell; male; phospholipid synthesis; prostate cancer; protein expression; protein function; protein lipid interaction; regulator gene; signal transduction; transcription regulation; umbilical vein endothelial cell; upregulation; vasculotropin C gene; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Human Umbilical Vein Endothelial Cells; Humans; Intercellular Signaling Peptides and Proteins; Lysophospholipids; Male; Phosphoric Diester Hydrolases; Prostatic Neoplasms; Reactive Oxygen Species; Receptors, Lysophosphatidic Acid; Vascular Endothelial Growth Factor C; Danio rerio
Type
journal article