title: Downregulation of activation factors of endothelia and fibroblasts via lysophosphatidic acid signaling in a mouse lung cancer LL/2 cell line.
abstract: Angiogenesis stimulates the invasive and metastatic process of cancer cells. It is also known that activated fibroblasts promote cancer cell growth and enhance invasive and metastatic potential. Lysophosphatidic acid (LPA) is a biological mediator and interacts with G protein-coupled transmembrane LPA receptors (LPA1 to LPA6). In this study, to assess an involvement of LPA3 on angiogenesis and fibroblast activation, the Lpar3-expressing cells were generated from mouse lung cancer LL/2 cells, which unexpressed LPA3. The Lpar3-expressing cells were maintained in serum-free Dulbecco's modified Eagle's medium for 48 h, and cell motility assay was performed with a cell culture Insert. When endothelial F-2 cells and 3T3 fibroblasts were cultured with conditioned medium from the Lpar3-expressing cells, their cell motile activities were significantly lower than the Lpar3-unexpressing (control) cells. Expression levels of vascular endothelial growth factor (Vegf) and fibroblast growth factor (Fgf) genes in the Lpar3-expressing cells were measured by quantitative real time reverse transcription polymerase chain reaction analysis. The expressions of Vegf-A. Fgfa and Fgfb genes in the Lpar3-expressing cells were significantly lower than those in control cells, correlating with the effects on cell motile activities of F-2 and 3T3 cells. These results suggest that LPA signaling through LPA3 may inhibit angiogenesis and fibroblast activation in mouse lung cancer cells.
authors.affiliation: Division of Cancer Biology and Bioinformatics and.
authors.forename: Eriko
authors.initials: E
authors.lastname: Tanabe
authors.forename: Misaho
authors.initials: M
authors.lastname: Kitayoshi
authors.forename: Miku
authors.initials: M
authors.lastname: Hirane
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Araki
authors.forename: Yan
authors.initials: Y
authors.lastname: Dong
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Fukushima
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Tsujiuchi
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002465:Cell Movement / Q000235:genetics; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008246:Lysophospholipids / Q000378:metabolism*; D051379:Mice; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis; D009374:Neoplasms, Experimental / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D049368:Receptors, Lysophosphatidic Acid / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics
chemical_list: D008246:Lysophospholipids; D049368:Receptors, Lysophosphatidic Acid; D042461:Vascular Endothelial Growth Factor A; C032881:lysophosphatidic acid