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Lysophosphatidic acid enhances VEGF‐C expression in PC‐3 human prostate cancer cells
Author(s) -
Lin Chuanen,
Lin ChihHsin,
Chang ChiLun,
Huang YuanLi,
Lee Hsinyu
Publication year - 2010
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.24.1_supplement.954.8
Subject(s) - lysophosphatidic acid , lymphangiogenesis , cancer cell , prostate cancer , cancer research , metastasis , vascular endothelial growth factor c , chemistry , biology , receptor , vascular endothelial growth factor , microbiology and biotechnology , cancer , vascular endothelial growth factor a , vegf receptors , biochemistry , genetics
Lysophosphatidic acid (LPA) is a low‐molecular‐weight lipid growth factor binds to G‐protein‐coupled receptors and activates a variety of physiological functions. VEGF‐C has been shown to regulate the development and growth of the lymphatic system. Our previous studies demonstrated that LPA enhances VEGF‐C in human endothelial cells, suggesting that LPA is an important regulator of lymphatic vessel formation and lymphangiogenesis. However, the roles of LPA on VEGF‐C expression on cancer cells were not elucidated. In this study, we showed that LPA up‐regulated VEGF‐C mRNA and protein expression in PC‐3 human prostate cancer cells. By using chemical inhibitors, we showed that these enhancement effects were LPA 1 ‐ and LPA 3 ‐dependent and required activation of Gi. To further confirm the roles of LPA on VEGF‐C expression in prostate cancer, PC‐3 cells stably expressed shRNA of LPA 1 and LPA 3 were generated. By real‐time PCR, we showed that the serum‐enhanced VEGF‐C expression is down‐regulated in these cell lines. Our results suggested that LPA regulates VEGF‐C expression in PC‐3 cells. This study provides some basic information that LPA might be a novel target for therapeutics against lymphangiogenesis and tumor metastasis.