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Metabolic Reprogramming in Colon Cancer Cells Persistently Infected with Newcastle Disease Virus
Tong Yu1, Archana Chandrabhan Jadhav2,3, Jiabao Xu1
1Department of Engineering Science, University of Oxford, Parks Road, Oxford OX1 3PJ, UK.
Cancers
|February 11, 2023
Summary
Newcastle disease virus (NDV) resistance in colon cancer cells involves metabolic reprogramming. Virus-resistant cells shift energy from DNA synthesis to protein and lipid production, impacting cancer therapy effectiveness.
Area of Science:
- Oncology
- Virology
- Biochemistry
Background:
- Newcastle disease virus (NDV) shows promise as an oncolytic agent for various mammalian cancers.
- Cancer cells can develop innate and acquired resistance to therapies, posing a significant challenge.
- Understanding resistance mechanisms is crucial for improving cancer treatment strategies.
Purpose of the Study:
- To investigate the metabolic adaptations in Caco-2 colon cancer cells that have developed resistance to Newcastle disease virus (NDV).
- To characterize the metabolic dynamics of virus-resistant (VR) Caco-2 cells using advanced spectroscopic techniques.
- To identify potential metabolic reprogramming events associated with NDV resistance.
Main Methods:
- Application of single-cell Raman spectroscopy combined with deuterium isotope probing (Raman-DIP) to analyze metabolic profiles.
- Utilizing linear discriminant analysis (LDA) for high-performance differentiation of resistant and non-resistant cancer cells at the single-cell level.
- Time-resolved comparative analysis of metabolic profiles between resistant and sensitive Caco-2 cell populations.
Main Results:
- A linear discriminant analysis (LDA) model effectively distinguished virus-resistant (VR) Caco-2 cells from standard Caco-2 cells.
- Metabolic profiling revealed upregulated de novo synthesis of proteins and lipids in VR Caco-2 cells.
- A decrease in DNA synthesis was observed in VR Caco-2 cells compared to their sensitive counterparts.
Conclusions:
- Virus-resistant (VR) Caco-2 cells exhibit significant metabolic reprogramming, diverting energy from proliferation.
- The observed metabolic shift favors protein synthesis and lipid modulation, contributing to NDV resistance.
- Characterizing resistant single cells aids in understanding resistance mechanisms and developing improved cancer therapies.
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