Related Experiment Video
Updated: Aug 10, 2025
Portal Vein Injection of Colorectal Cancer Organoids to Study the Liver Metastasis Stroma
Published on: September 3, 2021
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.
Abstract:
Newcastle disease virus (NDV) is an oncolytic agent against various types of mammalian cancers. As with all cancer therapies, the development of cancer resistance, both innate and acquired, is becoming a challenge. In this study, we investigated persistently NDV-infected Caco-2 colon cancer cells, designated as virus-resistant (VR) Caco-2 cells, which were then able to resist NDV-mediated oncolysis. We applied single-cell Raman spectroscopy, combined with deuterium isotope probing (Raman-DIP) techniques, to investigate the metabolic adaptations and dynamics in VR Caco-2 cells. A linear discriminant analysis (LDA) model demonstrated excellent performance in differentiating VR Caco-2 from Caco-2 cells at single-cell level. By comparing the metabolic profiles in a time-resolved manner, the de novo synthesis of proteins and lipids was found upregulated, along with decreased DNA synthesis in VR Caco-2. The results suggest that VR Caco-2 cells might reprogram their metabolism and divert energy from proliferation to protein synthesis and lipidic modulation. The ability to identify and characterise single resistant cells among a population of cancer cells would help develop a deeper understanding of the resistance mechanisms and better tactics for developing effective cancer treatment.
Insights
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.
Related Concept Videos
01:51Mechanisms of Retrovirus-induced Cancers
02:53Adaptive Mechanisms in Cancer Cells
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...