Lysophosphatidic acid enhances vascular endothelial growth factor-C expression in human prostate cancer PC-3 cells.
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 LPA(1/3)-dependent VEGF-C expression. Furthermore, autotaxin (ATX), an enzyme responsible for LPA synthesis, also participates in regulating VEGF-C expression. By interrupting LPA(1/3) 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 LPA(1/3)-, ROS-, and LEDGF-dependent pathways. These novel findings could potentially shed light on developing new strategies for preventing lymphatic metastasis of prostate cancer.
Institute of Zoology, National Taiwan University, Taipei, Taiwan, Republic of China.
Chuan-En
CE
Lin
Shee-Uan
SU
Chen
Chu-Cheng
CC
Lin
Chi-Hao
CH
Chang
Yueh-Chien
YC
Lin
Yu-Ling
YL
Tai
Tang-Long
TL
Shen
Hsinyu
H
Lee
D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008246:Lysophospholipids / Q000494:pharmacology*; D008297:Male; D010727:Phosphoric Diester Hydrolases / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D049368:Receptors, Lysophosphatidic Acid / Q000037:antagonists & inhibitors / Q000378:metabolism; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics / Q000378:metabolism*; D000099189:Lysophospholipase D
D036341:Intercellular Signaling Peptides and Proteins; D008246:Lysophospholipids; D010727:Phosphoric Diester Hydrolases; D017382:Reactive Oxygen Species; D049368:Receptors, Lysophosphatidic Acid; D042582:Vascular Endothelial Growth Factor C; D000099189:Lysophospholipase D; C119380:lens epithelium-derived growth factor; C032881:lysophosphatidic acid