Herpesvirus saimiri-based endothelin-converting enzyme-1 shRNA expression decreases prostate cancer cell invasion and migration

被引：9

作者：

Hong, Yue ^{[1
]}

Macnab, Stuart ^{[1
]}

Lambert, Louise A. ^{[1
]}

Turner, Anthony J. ^{[1
]}

Whitehouse, Adrian ^{[1
,2
]}

Usmani, Badar A. ^{[1
]}

机构：

[1] Univ Leeds, Inst Mol & Cellular Biol, Fac Biol Sci, Leeds LS2 9JT, W Yorkshire, England

[2] Univ Leeds, Astbury Ctr Struct Mol Biol, Leeds LS2 9JT, W Yorkshire, England

来源：

INTERNATIONAL JOURNAL OF CANCER | 2011年 / 129卷 / 03期

基金：

英国生物技术与生命科学研究理事会;

关键词：

prostate cancer; endothelin; endothelin-converting enzyme-1; Herpesvirus saimiri; metalloprotease; neprilysin; OVARIAN-CARCINOMA; VIRAL VECTOR; TUMOR-GROWTH; ECE-1; RECEPTOR; ISOFORMS; DELIVERY; THERAPY; LOCALIZATION; NEPRILYSIN;

D O I：

10.1002/ijc.25719

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The zinc metalloprotease, endothelin-converting enzyme-1 (ECE-1), which converts the mitogenic peptide endothelin-1 (ET-1) from its biologically inactive precursor big-ET-1, is commonly upregulated in prostate cancer (PC) cells. Consequently, we have sought to suppress ECE-1 expression by using RNAi as a potentially novel therapeutic approach. Therefore, a synthetic 64-nt short-hairpin RNA (shRNA), designed to target the ECE-1 gene, was expressed in an Herpesvirus saimiri (HVS)-based delivery vector. ECE-1 expression in cells transduced with the vector was examined by real-time PCR and Western blotting. The effects of ECE-1 knockdown on PC cell migration and invasion were studied using a scratch assay and Matrigel invasion. These studies, in vitro and ex vivo, demonstrated that the HVS-shRNA viruses could infect and silence ECE-1 expression effectively in human PC cells. Furthermore, it was observed that ECE-1 knockdown in either stromal cells or epithelial cells could significantly reduce invasion of PC-3 cells in coculture by 33 and 31%, respectively. In addition, suppressed migration was also observed in HVS-ECE-1 shRNA-infected PC-3 cells compared to uninfected and HVS-GFP-infected control cell cultures. These findings highlight the potential tumor-suppressing effect of ECE-1 knockdown in cancer cells and novel strategies for future therapeutic developments in advanced PC.

引用

页码：586 / 598

页数：13

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