Suppression of tumorigenicity by adenovirus-mediated gene transfer of decorin.
There is mounting evidence that decorin inhibits the growth of various tumor cell lines when either over-expressed in vitro or provided as a recombinant protein. The mechanism of action is primarily via a protracted inactivation of the epidermal growth factor receptor (EGFR) tyrosine kinase. In this study we explored the possibility of retarding the growth of tumor xenografts by decorin gene delivery into the growing neoplastic tissues. We demonstrate that transient transgene expression of replication-deficient adenovirus-containing decorin causes a significant growth inhibition of colon and squamous carcinoma tumor xenografts. These cytostatic effects were achieved with relatively low viral titers and correlated with a reduced proliferative index and an attenuation of the EGFR phosphorylation in vivo. Thus, decorin gene therapy helps in retarding the growth of human tumors in immunocompromised animals and could represent a new independent or adjunctive therapeutic modality against cancer.
Reed
Charles C
CC
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, PA 19107, USA.
Gauldie
Jack
J
Iozzo
Renato V
RV
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D019556:COS Cells; D002455:Cell Division; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology*; D058575:Decorin; D016326:Extracellular Matrix Proteins; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D016133:Polymerase Chain Reaction; D011509:Proteoglycans / Q000235:genetics* / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014161:Transduction, Genetic; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
C546878:DCN protein, human; C546879:Dcn protein, mouse; D058575:Decorin; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; D012333:RNA, Messenger