Lysophosphatidic acid downregulates tissue inhibitor of metalloproteinases, which are negatively involved in lysophosphatidic acid-induced cell invasion

摘要: Ovarian cancer is a highly metastatic disease. Lysophosphatidic acid (LPA) levels are elevated in ascites from ovarian patients, but its potential role metastasis has just begun to be revealed. In this work, we show that LPA stimulates invasion of primary cells, not epithelial or borderline tumor although these benign cells indeed respond cell migration. We have found downregulates tissue inhibitor metalloproteinases (TIMPs). TIMP2 and TIMP3 play functional LPA-induced as negative regulators. Gi protein, phosphatidylinositol-3 kinase (PI3K), p38 mitogen-activated protein (MAPK), cytosolic phospholipase A2 urokinase type plasminogen activator (uPA) required for invasion. may affect two independent downstream targets, vascular endothelial growth factor receptor MAPK. vivo, an orthotopic model, which can inhibited by PI3K inhibitor, LY294002. summary, likely key component promoting vivo. TIMP3, targets other than metalloproteinases. Our vivo mouse model useful studying the efficacy therapeutic regimes cancer.