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

Li, Mei-Hong; Sanchez, Teresa; Yamase, Harold; Hla, Timothy; Oo, Myat Lin; Pappalardo, Anna; Lynch, Kevin R.; Lin, Chen-Yong; Ferrer, Fernando

doi:10.1016/j.canlet.2008.11.025

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Volume 276, Issue 2 , Pages 171-179, 18 April 2009

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

Mei-Hong Li
- Center for Vascular Biology, University of Connecticut Health Center, Farmington, CT 06030, United States
- Department of Surgery, Division of Urology, Connecticut Children’s Medical Center, Suite 2E, 282 Washington Street, Hartford, CT 06106, United States
Teresa Sanchez
- Center for Vascular Biology, University of Connecticut Health Center, Farmington, CT 06030, United States
Harold Yamase
- Department of Pathology and Laboratory Medicine, University of Connecticut Health Center, Farmington, CT 06030, United States
Timothy Hla
- Center for Vascular Biology, University of Connecticut Health Center, Farmington, CT 06030, United States
Myat Lin Oo
- Center for Vascular Biology, University of Connecticut Health Center, Farmington, CT 06030, United States
Anna Pappalardo
- Center for Vascular Biology, University of Connecticut Health Center, Farmington, CT 06030, United States
- Department of Surgery, Division of Urology, Connecticut Children’s Medical Center, Suite 2E, 282 Washington Street, Hartford, CT 06106, United States
Kevin R. Lynch
- Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, United States
Chen-Yong Lin
- Lombardi Cancer Center, Georgetown University School of Medicine, Washington, DC 20007, United States
Fernando Ferrer
- Center for Vascular Biology, University of Connecticut Health Center, Farmington, CT 06030, United States
- Department of Surgery, Division of Urology, Connecticut Children’s Medical Center, Suite 2E, 282 Washington Street, Hartford, CT 06106, United States
- Corresponding author. Address: Department of Surgery, Division of Urology, Connecticut Children’s Medical Center, Suite 2E, 282 Washington Street, Hartford, CT 06106, United States. Tel.: +1 860 545 9658; fax: +1 860 545 9545.

Received 16 July 2008; received in revised form 19 September 2008; accepted 7 November 2008. published online 09 January 2009.

Abstract

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 S1P₁ acted as a promigratory modulator by employing S1P₁ antagonist VPC44116, S1P₁ siRNA and adenoviral transduction in Wilms tumor cells. Further, we clarified that S1P₁-mediated migration occurred via Gi coupling and activation of PI3K and Rac1. In addition, S1P stimulated WiT49 cell invasion through S1P₁/Gi signaling pathway. We consider that targeting S1P₁ may be a point of therapeutic intervention in Wilms tumor.

Keywords: Migration, Invasion, Sphingosine 1-phosphate, WiT49, Wilms tumor