High Glucose Induces Aerobic Glycolysis and Vascular Endothelial Growth Factor‐C through LPA Signals in Human Prostate Cancer PC‐3 Cells

Abstract

Prostate cancer is one of the most commonly diagnosed cancers in males and frequently metastasizes to lymph nodes. Clinical evidences suggested that type II diabetes mellitus were closely associated with the prognosis of prostate cancer. Furthermore, hyperglycemia increases aerobic glycolysis and promote cancer growth. However, the effects of hyperglycemia in prostate cancer remain elusive. Lysophosphatidic acid (LPA) is a small lipid growth factor with multiple functions by activating G‐protein coupled LPA receptors. We demonstrated that LPA enhance VEGF‐C expression through activating LPA receptor 1 and 3 in prostate cancer cells. Furthermore, high glucose treatment has also been shown to enhance VEGF‐C expression in human synovial fibroblasts. In this study, we used PC‐3 cell to investigate whether high glucose induces VEGF‐C expression and aerobic glycolysis through LPA signals to enhance cancer progression. Our preliminary results demonstrated that the mRNA expression level of autotaxin (ATX), an enzyme responsible for LPA synthesis, was increased in PC‐3 cell by 0.02 M glucose treatments. Protein levels of VEGF‐C were also increased after high glucose treatments. Furthermore, the enhancement of VEGF‐C was mediated through ROS‐ and LEDGF‐dependent pathways. On the other hand, high glucose treatments also enhanced aerobic glycolysis rate and affected mRNA expression levels of glucose transporter and hexokinase. Taken together, these results suggested that unregulated glucose metabolism might lead to LPA synthesis and therefore subsequent pathological conditions of prostate cancer.