Comparative protein profiling of B16 mouse melanoma cells susceptible and non-susceptible to alphavirus infection: Effect of the tumor microenvironment
| Autor: | Dmitry Zhulenvovs, Raimonds Paplausks, Maria Stensland, Tatjana Kozlovska, Baiba Kurena, Gustavo A. de Souza, Jelena Vasilevska, Anna Zajakina, Dace Skrastina |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Pharmacology Cancer Research Tumor microenvironment Alphavirus Biology Proteomics biology.organism_classification In vitro Cell biology 03 medical and health sciences Transduction (genetics) 030104 developmental biology 0302 clinical medicine Oncology Viral entry 030220 oncology & carcinogenesis Gene expression Molecular Medicine Corrigendum Intracellular Research Paper |
| Zdroj: | Cancer Biology & Therapy. 17:1035-1050 |
| ISSN: | 1555-8576 1538-4047 |
| DOI: | 10.1080/15384047.2016.1219813 |
| Popis: | Alphavirus vectors are promising tools for cancer treatment. However, relevant entry mechanisms and interactions with host cells are still not clearly understood. The first step toward a more effective therapy is the identification of novel intracellular alterations that could be associated with cancer aggressiveness and could affect the therapeutic potential of these vectors. In this study, we observed that alphaviruses efficiently infected B16 mouse melanoma tumors/tumor cells in vivo, whereas their transduction efficiency in B16 cells under in vitro conditions was blocked. Therefore, we further aimed to understand the mechanisms pertaining to the differential transduction efficacy of alphaviruses in B16 tumor cells under varying growth conditions. We hypothesized that the tumor microenvironment might alter gene expression in B16 cells, leading to an up-regulation of the expression of virus-binding receptors or factors associated with virus entry and replication. To test our hypothesis, we performed a proteomics analysis of B16 cells cultured in vitro and of B16 cells isolated from tumors, and we identified 277 differentially regulated proteins. A further in-depth analysis to identify the biological and molecular functions of the detected proteins revealed a set of candidate genes that could affect virus infectivity. Importantly, we observed a decrease in the expression of interferon α (IFN-α) in tumor-isolated cells that resulted in the suppression of several IFN-regulated genes, thereby abrogating host cell antiviral defense. Additionally, differences in the expression of genes that regulate cytoskeletal organization caused significant alterations in cell membrane elasticity. Taken together, our findings demonstrated favorable intracellular conditions for alphavirus transduction/replication that occurred during tumor transformation. These results pave the way for optimizing the development of strategies for the application of alphaviral vectors as a potent cancer therapy. |
| Databáze: | OpenAIRE |
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