In Vivo Selective and Distant Killing of Cancer Cells Using Adenovirus-mediated Decorin Gene Transfer

Overview

Journal FASEB J

Specialties Biology
Physiology

Date 2003 Mar 13

PMID 12631584

Citations 54

Authors

J Guilherme Tralhao

Liliana Schaefer

Miroslava Micegova

Cesar Evaristo

Elke Schonherr

Samer Kayal

Henrique Veiga-Fernandes

Claire Danel

Renato V Iozzo

Hans Kresse

Patricia Lemarchand

Affiliations

Soon will be listed here.

Abstract

Decorin is a well-known, ubiquitous proteoglycan that is a normal component of the ECM. Upon transgenic expression of decorin, tumor cells with diverse histogenetic background overexpress p21WAF1, a potent inhibitor of cyclin-dependent kinase activity, become arrested in G1, and fail to generate tumors in immunocompromised animals. Because decorin is a secreted protein, it has been recently suggested that decorin could act as an autocrine and paracrine regulator of tumor growth. Here, we demonstrate that adenovirus (Ad)-mediated transfer and expression of human decorin cDNA induced in vivo apoptosis of xenograft tumor cells in nude mice. This oncolytic activity was observed when the Ad vector encoding the decorin cDNA was injected intratumorally (i.t.) or i.v. Importantly, i.t. injection of the decorin Ad vector led to growth inhibition of the injected tumor associated with similar growth inhibition of a distant contralateral tumor, demonstrating a distant decorin antitumoral effect. Immunochemistry against human decorin and decorin quantitation in tumors confirmed that decorin migrated to the tumor distant site. Furthermore, decorin effect was specific to tumor cells, because neither apoptosis nor growth inhibition were observed in nontumoral human cells such as hepatocytes, endothelial cells, and fibroblasts, despite p21 overexpression.

Citing Articles

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