Park Kyoung Sun, Kim Mi-Kyoung, Lee Ha Young, Kim Sang Doo, Lee Sun Young, Kim Jung Mo, Ryu Sung Ho, Bae Yoe-Sik
Department of Biochemistry, College of Medicine, Dong-A University, Busan 602-714, Republic of Korea.
Biochem Biophys Res Commun. 2007 Apr 27;356(1):239-44. doi: 10.1016/j.bbrc.2007.02.112. Epub 2007 Feb 28.
OVCAR3 ovarian cancer cells express three sphingosine 1-phosphate (S1P) receptors, S1P(1), S1P(2), and S1P(3), but not S1P(4). Stimulation of OVCAR3 cells with S1P induced intracellular calcium increases, which were partly inhibited by VPC 23019 (an S1P(1/3) antagonist). S1P-induced calcium increases were mediated by phospholipase C and pertussis toxin (PTX)-sensitive G-proteins in OVCAR3 cells. S1P stimulated extracellular signal-regulated kinase, p38 kinase, and Akt which were inhibited by PTX. S1P-stimulated chemotactic migration of OVCAR3 cells in a PTX-sensitive manner, indicating crucial role of G(i) protein(s) in the process. S1P-induced chemotactic migration of OVCAR3 cells was completely inhibited by LY294002 and SB203580. Pretreatment of VPC 23019 (an S1P(1/3) antagonist) completely inhibited S1P-induced chemotaxis. S1P also induced invasion of OVCAR3 cells, which was also inhibited by VPC 23019. Taken together, this study suggests that S1P stimulate chemotactic migration and cellular invasion, and VPC 23019-sensitive S1P receptor(s) might be involved in the processes.
OVCAR3卵巢癌细胞表达三种1-磷酸鞘氨醇（S1P）受体，即S1P(1)、S1P(2)和S1P(3)，但不表达S1P(4)。用S1P刺激OVCAR3细胞会导致细胞内钙增加，而VPC 23019（一种S1P(1/3)拮抗剂）可部分抑制这种增加。S1P诱导的钙增加在OVCAR3细胞中是由磷脂酶C和百日咳毒素（PTX）敏感的G蛋白介导的。S1P刺激细胞外信号调节激酶、p38激酶和Akt，这些均被PTX抑制。S1P以PTX敏感的方式刺激OVCAR3细胞的趋化迁移，表明G(i)蛋白在此过程中起关键作用。S1P诱导的OVCAR3细胞趋化迁移被LY294002和SB203580完全抑制。VPC 23019（一种S1P(1/3)拮抗剂）预处理可完全抑制S1P诱导的趋化作用。S1P还诱导OVCAR3细胞侵袭，这也被VPC 23019抑制。综上所述，本研究表明S1P刺激趋化迁移和细胞侵袭，且对VPC 23019敏感的S1P受体可能参与了这些过程。
