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Published on: July 30, 2018
Suppression of tumorigenicity by adenovirus-mediated gene transfer of decorin
Charles C Reed1, Jack Gauldie, Renato V Iozzo
1Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, PA 19107, USA.
Abstract:
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.
Insights
Decorin gene therapy significantly inhibits tumor xenograft growth by targeting the epidermal growth factor receptor (EGFR). This approach offers a potential new treatment for various cancers.
Area of Science:
- Oncology
- Gene Therapy
- Molecular Biology
Background:
- Decorin is known to inhibit tumor cell growth in vitro and via recombinant protein administration.
- Its primary mechanism involves the prolonged inactivation of epidermal growth factor receptor (EGFR) tyrosine kinase.
Purpose of the Study:
- To investigate the potential of decorin gene delivery for retarding tumor xenograft growth.
- To assess the efficacy of decorin gene therapy in vivo.
Main Methods:
- Utilized replication-deficient adenovirus vectors for transient decorin transgene expression.
- Administered decorin gene delivery directly into established tumor xenografts in immunocompromised animals.
- Monitored tumor growth, proliferative index, and EGFR phosphorylation levels.
Main Results:
- Transient decorin gene expression significantly inhibited the growth of colon and squamous carcinoma xenografts.
- Cytostatic effects were observed even at relatively low viral titers.
- Correlated growth inhibition with a reduced proliferative index and attenuated EGFR phosphorylation in vivo.
Conclusions:
- Decorin gene therapy demonstrates efficacy in retarding human tumor growth in animal models.
- This approach represents a promising therapeutic strategy, potentially as a standalone or adjunctive cancer treatment.
- Targeting EGFR through decorin gene delivery offers a novel avenue for cancer therapy.
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