Open AccessVascular endothelial growth factor promoter‐based conditionally replicative adenoviruses effectively suppress growth of malignant pleural mesothelioma
Author(s) -
Harada Akiko,
Uchino Junji,
Harada Taishi,
Nakagaki Noriaki,
Hisasue Junko,
Fujita Masaki,
Takayama Koichi
Publication year - 2017
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13112
Subject(s) - oncolytic virus , mesothelioma , vascular endothelial growth factor , cancer research , medicine , oncolytic adenovirus , in vivo , pleural disease , pathology , vegf receptors , respiratory disease , lung , biology , tumor cells , microbiology and biotechnology
Malignant mesothelioma ( MM ) incidence is increasing drastically worldwide as an occupational disease resulting from asbestos exposure. However, no curative treatment for MM of advanced stage is available. Thus, new therapeutic approaches for MM are required. Because malignant pleural mesothelioma ( MPM ) cells spread along the pleural surface in most patients, MPM can be targeted using intrapleural therapeutic approaches. In this study, we investigated the effectiveness of the intrapleural instillation of a replication‐competent adenovirus as an oncolytic agent against MPM . We constructed a vascular endothelial growth factor promoter‐based conditionally replicative adenovirus ( VEGF ‐ CRA d) that replicates exclusively in VEGF ‐expressing cells. All of the MM cell lines that we tested expressed VEGF mRNA , and VEGF ‐ CRA d selectively replicated in these MM cells and exerted a direct concentration‐dependent oncolytic effect in vitro . Furthermore, our in vivo studies showed that pre‐infection of MM cells with VEGF ‐ CRA d potently suppressed MPM tumor formation in nude mice, and that intrapleural instillation of VEGF ‐ CRA d prolonged the survival time of tumor‐bearing mice. Our results indicate that VEGF ‐ CRA d exerts an oncolytic effect on MM cells and that intrapleural instillation of VEGF ‐ CRA d is safe and might represent a promising therapeutic strategy for MPM .