Vasoactive intestinal peptide (VIP) induces malignant transformation of the human prostate epithelial cell line RWPE-1

Fernández-Martínez, Ana B.; Bajo, Ana M.; Isabel Arenas, M.; Sánchez-Chapado, Manuel; Prieto, Juan C.; Carmena, María J.

doi:10.1016/j.canlet.2010.07.019

« Previous Next »Cancer Letters
Volume 299, Issue 1 , Pages 11-21, 18 December 2010

Vasoactive intestinal peptide (VIP) induces malignant transformation of the human prostate epithelial cell line RWPE-1

Ana B. Fernández-Martínez
- Department of Biochemistry and Molecular Biology, University of Alcalá, 28871 Alcalá de Henares, Spain
Ana M. Bajo
- Department of Biochemistry and Molecular Biology, University of Alcalá, 28871 Alcalá de Henares, Spain
M. Isabel Arenas
- Department of Cell Biology and Genetics, University of Alcalá, 28871 Alcalá de Henares, Spain
Manuel Sánchez-Chapado
- Department of Surgery, University of Alcalá, 28871 Alcalá de Henares, Spain
- Department of Urology, Príncipe de Asturias Hospital, 28871 Alcalá de Henares, Spain
Juan C. Prieto
- Department of Biochemistry and Molecular Biology, University of Alcalá, 28871 Alcalá de Henares, Spain
- Corresponding author. Tel.: +34 91 885 4527; fax: +34 91 885 4585.
María J. Carmena
- Department of Biochemistry and Molecular Biology, University of Alcalá, 28871 Alcalá de Henares, Spain

Received 8 June 2010; received in revised form 20 July 2010; accepted 22 July 2010. published online 16 August 2010.

Abstract

The carcinogenic potential of vasoactive intestinal peptide (VIP) was analyzed in non-tumor human prostate epithelial cells (RWPE-1) and in vivo xenografts. VIP induced morphological changes and a migratory phenotype consistent with stimulation of expression/activity of metalloproteinases MMP-2 and MMP-9, decreased E-cadherin-mediated cell–cell adhesion, and increased cell motility. VIP increased cyclin D1 expression and cell proliferation that was blocked after VPAC₁-receptor siRNA transfection. Similar effects were seen in RWPE-1 tumors developed by subcutaneous injection of VIP-treated cells in athymic nude mice. VIP acts as a cytokine in RWPE-1 cell transformation conceivably through epithelial–mesenchymal transition (EMT), reinforcing VIP role in prostate tumorigenesis.

Keywords: VIP, RWPE-1 cells, EMT, Tumorigenesis, Prostate cancer