Adenovirus-Mediated Expression of the p14 Fusion-Associated Small Transmembrane Protein Promotes Cancer Cell Fusion and Apoptosis In Vitro but Does Not Provide Therapeutic Efficacy in a Xenograft Mouse Model of Cancer
| العنوان: | Adenovirus-Mediated Expression of the p14 Fusion-Associated Small Transmembrane Protein Promotes Cancer Cell Fusion and Apoptosis In Vitro but Does Not Provide Therapeutic Efficacy in a Xenograft Mouse Model of Cancer |
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| المؤلفون: | Kathy L. Poulin, John C. Bell, Grace Tong, Carmen M. Wong, Theresa Falls, Robin J. Parks, Michael A. Kennedy, Carin Christou |
| المصدر: | PLoS ONE, Vol 11, Iss 3, p e0151516 (2016) PLoS ONE |
| بيانات النشر: | Public Library of Science (PLoS), 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, Cell, Protein Expression, Cell Membranes, lcsh:Medicine, Apoptosis, Viral Nonstructural Proteins, Biochemistry, Cell Fusion, 0302 clinical medicine, Nude mouse, Neoplasms, Cytotoxic T cell, lcsh:Science, Protein Metabolism, Syncytium, Multidisciplinary, Cell fusion, Cell Death, 3. Good health, medicine.anatomical_structure, Cell Processes, 030220 oncology & carcinogenesis, Cell lines, Cellular Structures and Organelles, Biological cultures, Research Article, Cell Physiology, Cell Survival, Blotting, Western, Genetic Vectors, Mice, Nude, Biology, Research and Analysis Methods, Reoviridae, Adenoviridae, 03 medical and health sciences, Cell Line, Tumor, medicine, Gene Expression and Vector Techniques, Animals, Humans, Molecular Biology Techniques, Molecular Biology, A549 cell, Molecular Biology Assays and Analysis Techniques, HEK 293 cells, lcsh:R, Biology and Life Sciences, Membrane Proteins, Cell Biology, Genetic Therapy, biology.organism_classification, Molecular biology, Xenograft Model Antitumor Assays, Cell Metabolism, 030104 developmental biology, Metabolism, HEK293 Cells, Microscopy, Fluorescence, Cancer cell, Cancer research, lcsh:Q, Viral Fusion Proteins |
| الوصف: | Adenoviruses (Ads) are used in numerous preclinical and clinical studies for delivery of anti-cancer therapeutic genes. Unfortunately, Ad has a poor ability to distribute throughout a tumor mass after intratumoral injection, and infects cells primarily within the immediate area of the injection tract. Thus, Ad-encoded transgene expression is typically limited to only a small percentage of cells within the tumor. One method to increase the proportion of the tumor impacted by Ad is through expression of fusogenic proteins. Infection of a single cell with an Ad vector encoding a fusogenic protein should lead to syncytium formation with adjacent cells, effectively spreading the effect of Ad and Ad-encoded therapeutic transgenes to a greater percentage of the tumor mass. Moreover, syncytium formation can be cytotoxic, suggesting that such proteins may be effective sole therapeutics. We show that an early region 1 (E1)-deleted Ad expressing reptilian reovirus p14 fusion-associated small transmembrane (FAST) protein caused extensive cell fusion in the replication-permissive 293 cell line and at high multiplicity of infection in non-permissive human lung adenocarcinoma A549 cells in vitro. FAST protein expression in the A549 cancer cell line led to a loss of cellular metabolic activity and membrane integrity, which correlated with induction of apoptosis. However, in an A549 xenograft CD-1 nude mouse cancer model, Ad-mediated FAST gene delivery did not induce detectable cell fusion, reduce tumor burden nor enhance mouse survival compared to controls. Taken together, our results show that, although AdFAST can enhance cancer cell killing in vitro, it is not effective as a sole therapeutic in the A549 tumor model in vivo. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dc3e4d5ecab7e73c63b114511f288056 http://europepmc.org/articles/PMC4795661?pdf=render |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....dc3e4d5ecab7e73c63b114511f288056 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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