AIM: To explore the role of lysophosphatidic acid receptor-2 (LPA2) in regulating lysophosphatidic acid (LPA)-induced urokinase plasminogen activator (uPA) activation, cell invasion, and migration in human ovarian cancer cell line SKOV-3. METHODS: SKOV-3 cells were stimulated with LPA. Cell supernatant uPA level and activity were measured using enzyme-linked immunosorbent assay. LPA2 mRNA expression was inhibited with LPA2-specific small interfering RNA (siRNA) and examined using semiquantitative reverse transcriptase-polymerase chain reaction. LPA-induced cell invasion and migration in transfected cells were evaluated by a Matrigel invasion chamber and a Transwell chemotaxis chamber, respectively. RESULTS: LPA stimulation significantly enhanced in vitro uPA activity in time- and dose-dependent manner. The levels of LPA-induced uPA protein decreased by 55% in LPA2 siRNA-transfected cells compared with negatively transfected cells at 24 hours after being treated with 80 micromol/L LPA (0.75+/-0.03 vs 0.34+/-0.04, P=0.004). In the LPA2 specific siRNA-transfected SKOV-3 cells, LPA treatment at 80 micromol/L induced considerably less invasion and migration compared with negative control siRNA-transfected SKOV-3 cells (invasion: 178+/-17.2 vs 36.2+/-3.3, P=0.009; migration: 220.4+/-25.5 vs 57+/-7.6, P=0.009). CONCLUSION: LPA2 has an essential role in LPA-induced uPA activation and tumor cell invasion in ovarian cancer SKOV-3 cells.
AIM: To explore the role of lysophosphatidic acid receptor-2 (LPA2) in regulating lysophosphatidic acid (LPA)-induced urokinase plasminogen activator (uPA) activation, cell invasion, and migration in humanovarian cancer cell line SKOV-3. METHODS: SKOV-3 cells were stimulated with LPA. Cell supernatant uPA level and activity were measured using enzyme-linked immunosorbent assay. LPA2 mRNA expression was inhibited with LPA2-specific small interfering RNA (siRNA) and examined using semiquantitative reverse transcriptase-polymerase chain reaction. LPA-induced cell invasion and migration in transfected cells were evaluated by a Matrigel invasion chamber and a Transwell chemotaxis chamber, respectively. RESULTS:LPA stimulation significantly enhanced in vitro uPA activity in time- and dose-dependent manner. The levels of LPA-induced uPA protein decreased by 55% in LPA2 siRNA-transfected cells compared with negatively transfected cells at 24 hours after being treated with 80 micromol/L LPA (0.75+/-0.03 vs 0.34+/-0.04, P=0.004). In the LPA2 specific siRNA-transfected SKOV-3 cells, LPA treatment at 80 micromol/L induced considerably less invasion and migration compared with negative control siRNA-transfected SKOV-3 cells (invasion: 178+/-17.2 vs 36.2+/-3.3, P=0.009; migration: 220.4+/-25.5 vs 57+/-7.6, P=0.009). CONCLUSION:LPA2 has an essential role in LPA-induced uPA activation and tumor cell invasion in ovarian cancer SKOV-3 cells.
Authors: T B Pustilnik; V Estrella; J R Wiener; M Mao; A Eder; M A Watt; R C Bast; G B Mills Journal: Clin Cancer Res Date: 1999-11 Impact factor: 12.531
Authors: W Siess; K J Zangl; M Essler; M Bauer; R Brandl; C Corrinth; R Bittman; G Tigyi; M Aepfelbacher Journal: Proc Natl Acad Sci U S A Date: 1999-06-08 Impact factor: 11.205
Authors: Xianjun Fang; Michel Schummer; Muling Mao; Shuangxing Yu; Fazal Haq Tabassam; Ramona Swaby; Yutaka Hasegawa; Janos L Tanyi; Ruthie LaPushin; Astrid Eder; Robert Jaffe; Jim Erickson; Gordon B Mills Journal: Biochim Biophys Acta Date: 2002-05-23
Authors: Thomas M McIntyre; Aaron V Pontsler; Adriana R Silva; Andy St Hilaire; Yong Xu; Jerald C Hinshaw; Guy A Zimmerman; Kotaro Hama; Junken Aoki; Hiroyuki Arai; Glenn D Prestwich Journal: Proc Natl Acad Sci U S A Date: 2002-12-26 Impact factor: 11.205