Premium
Lysophosphatidic acid‐Autotaxin Axis Enhances VEGF‐C EXpression in Human Prostate Cancer
Author(s) -
Lin Chuanen,
Lin JiuJenq,
Chang ChiHao,
Chiang Chiling,
Lee Hsinyu
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.243.2
Subject(s) - lymphangiogenesis , lysophosphatidic acid , prostate cancer , cancer research , metastasis , vascular endothelial growth factor c , cancer , cancer cell , biology , lymphatic system , vascular endothelial growth factor , microbiology and biotechnology , medicine , vascular endothelial growth factor a , receptor , immunology , vegf receptors
Many clinical evidences suggested that prostate cancer, one of the most frequent occurred cancers in male, induces lymphangiogenesis and enhances lymphatic metastasis. Lymphangiogenesis is a process of new lymphatic vessel formation. Vascular Endothelial Growth Factor C (VEGF‐C) has been shown to be a key regulator in this process. Our previous studies demonstrated that LPA, a low molecular weight lipid growth factor enhances VEGF‐C in human endothelial cells. We also showed LPA receptor plays an important role in lymphatic development in zebrafish embryo. However, the roles of LPA on VEGF‐C expression in prostate cancer were not elucidated. In our results, we showed that LPA upregulated VEGF‐C mRNA in different human prostate cancer cell lines. We also clarified that these enhancement effects in PC‐3 were mediated through both LPA1 and LPA3. Furthermore, ROS production and LEDGF expression were identified to participate in LPA1/3 dependent VEGF‐C expression. ATX, an enzyme synthesizing LPA was discovered to self‐regulate VEGF‐C mRNA and secretion expression. In summary, PC‐3 cells could secret LPA for postitive‐regulating VEGF‐C through LPA1/3, ROS and LEDGF dependent pathway. The unprecedented finding could potentially shed light on developing new strategy for preventing prostate cancer lymphatic metastasis.