Linked Life Data

17130843

Source:http://linkedlifedata.com/resource/pubmed/id/17130843

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
20
pubmed:dateCreated
2007-5-3
pubmed:abstractText
Ovarian cancer is a highly metastatic disease. Lysophosphatidic acid (LPA) levels are elevated in ascites from ovarian cancer patients, but its potential role in ovarian cancer metastasis has just begun to be revealed. In this work, we show that LPA stimulates invasion of primary ovarian cancer cells, but not ovarian epithelial or borderline ovarian tumor cells, although these benign cells indeed respond to LPA in cell migration. We have found that LPA downregulates tissue inhibitor of metalloproteinases (TIMPs). TIMP2 and TIMP3 play functional role in LPA-induced invasion as negative regulators. G(i) protein, phosphatidylinositol-3 kinase (PI3K), p38 mitogen-activated protein kinase (MAPK), cytosolic phospholipase A(2) and urokinase type plasminogen activator (uPA) are required for LPA-induced cells invasion. TIMP3 may affect two independent downstream targets, vascular endothelial growth factor receptor and p38 MAPK. In vivo, LPA stimulates tumor metastasis in an orthotopic ovarian tumor model, which can be inhibited by a PI3K inhibitor, LY294002. In summary, LPA is likely a key component for promoting ovarian metastasis in vivo. LPA downregulates TIMP3, which may have targets other than metalloproteinases. Our in vivo metastasis mouse model is useful for studying the efficacy of therapeutic regimes of ovarian cancer.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
3
pubmed:volume
26
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2894-901
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:17130843-Animals, pubmed-meshheading:17130843-Cell Movement, pubmed-meshheading:17130843-Epithelial Cells, pubmed-meshheading:17130843-Female, pubmed-meshheading:17130843-GTP-Binding Protein alpha Subunits, Gi-Go, pubmed-meshheading:17130843-Gene Expression Regulation, Neoplastic, pubmed-meshheading:17130843-Humans, pubmed-meshheading:17130843-Lysophospholipids, pubmed-meshheading:17130843-Mice, pubmed-meshheading:17130843-Neoplasm Invasiveness, pubmed-meshheading:17130843-Neoplasm Metastasis, pubmed-meshheading:17130843-Ovarian Neoplasms, pubmed-meshheading:17130843-Phosphatidylinositol 3-Kinases, pubmed-meshheading:17130843-Tissue Inhibitor of Metalloproteinases, pubmed-meshheading:17130843-Tumor Cells, Cultured, pubmed-meshheading:17130843-Xenograft Model Antitumor Assays, pubmed-meshheading:17130843-p38 Mitogen-Activated Protein Kinases
pubmed:year
2007
pubmed:articleTitle
Lysophosphatidic acid downregulates tissue inhibitor of metalloproteinases, which are negatively involved in lysophosphatidic acid-induced cell invasion.
pubmed:affiliation
Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural