S1P/S1P1 signaling stimulates cell migration and invasion in Wilms tumor

被引:53
作者
Li, Mei-Hong [1 ,2 ]
Sanchez, Teresa [2 ]
Yamase, Harold [3 ]
Hla, Timothy [2 ]
Oo, Myat Lin [2 ]
Pappalardo, Anna [1 ,2 ]
Lynch, Kevin R. [4 ]
Lin, Chen-Yong [5 ]
Ferrer, Fernando [1 ,2 ]
机构
[1] Connecticut Childrens Med Ctr, Div Urol, Dept Surg, Hartford, CT 06106 USA
[2] Univ Connecticut, Ctr Hlth, Ctr Vasc Biol, Farmington, CT 06030 USA
[3] Univ Connecticut, Ctr Hlth, Dept Pathol & Lab Med, Farmington, CT 06030 USA
[4] Univ Virginia, Dept Pharmacol, Charlottesville, VA 22908 USA
[5] Georgetown Univ, Sch Med, Lombardi Canc Ctr, Washington, DC 20007 USA
关键词
Migration; Invasion; Sphingosine; 1-phosphate; WiT49; Wilms tumor; PROTEIN-COUPLED RECEPTOR; SPHINGOSINE 1-PHOSPHATE RECEPTOR-1; SPHINGOSINE-1-PHOSPHATE RECEPTORS; CANCER CELLS; DIFFERENTIAL REGULATION; VASCULAR-PERMEABILITY; EXPRESSION PROFILE; ENDOTHELIAL-CELLS; FTY720; GROWTH;
D O I
10.1016/j.canlet.2008.11.025
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Sphingosine-1-phosphate (S1P) is an important regulator of cellular functions via interaction with its receptors S1P(1-5). To date, nothing is known about the S1P receptor expression and the effects of S1P signaling in Wilms tumor. In this study, we found ubiquitous expression of S1P receptors in Wilms tumor specimens and cell lines. We demonstrated that S1P(1) acted as a promigratory modulator by employing S1P(1) antagonist VPC44116, S1P(1) siRNA and adenoviral transduction in Wilms tumor cells. Further, we clarified that S1P(1)-mediated migration occurred via Gi coupling and activation of PI3K and Rac1. In addition, S1P stimulated WiT49 cell invasion through S1P(1)/Gi signaling pathway. We consider that targeting S1P(1) may be a point of therapeutic intervention in Wilms tumor. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:171 / 179
页数:9
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