Multi-Omics Analysis of Glioblastoma Cells' Sensitivity to Oncolytic Viruses.
Anastasiya V LipatovaAlesya V SobolevaVladimir A GorshkovJulia A BubisElizaveta M SolovyevaGeorge S KrasnovDmitry V KochetkovPavel O VorobyevIrina Y IlinaSergei A MoshkovskiiFrank KjeldsenMikhail V GorshkovPeter M ChumakovIrina A TarasovaPublished in: Cancers (2021)
Oncolytic viruses have gained momentum in the last decades as a promising tool for cancer treatment. Despite the progress, only a fraction of patients show a positive response to viral therapy. One of the key variable factors contributing to therapy outcomes is interferon-dependent antiviral mechanisms in tumor cells. Here, we evaluated this factor using patient-derived glioblastoma multiforme (GBM) cultures. Cell response to the type I interferons' (IFNs) stimulation was characterized at mRNA and protein levels. Omics analysis revealed that GBM cells overexpress interferon-stimulated genes (ISGs) and upregulate their proteins, similar to the normal cells. A conserved molecular pattern unambiguously differentiates between the preserved and defective responses. Comparing ISGs' portraits with titration-based measurements of cell sensitivity to a panel of viruses, the "strength" of IFN-induced resistance acquired by GBM cells was ranked. The study demonstrates that suppressing a single ISG and encoding an essential antiviral protein, does not necessarily increase sensitivity to viruses. Conversely, silencing IFIT3 and PLSCR1 genes in tumor cells can negatively affect the internalization of vesicular stomatitis and Newcastle disease viruses. We present evidence of a complex relationship between the interferon response genes and other factors affecting the sensitivity of tumor cells to viruses.
Keyphrases
- induced apoptosis
- cell cycle arrest
- single cell
- dendritic cells
- signaling pathway
- cell therapy
- immune response
- genome wide
- endoplasmic reticulum stress
- stem cells
- gene expression
- cell death
- cell proliferation
- prognostic factors
- genetic diversity
- high glucose
- type diabetes
- pi k akt
- diabetic rats
- binding protein
- mesenchymal stem cells
- insulin resistance
- endothelial cells
- drug induced