Metabolic Recycling Enhances Proliferation in MYC-Transformed Lymphoma B Cells

Cissy Zhang, Giang Hoang, Nabeel Attarwala, Arthur J.L. Cooper, Ryoichi Asaka, Anne Le

Research output: Contribution to journalArticlepeer-review

Abstract

Relapses negatively impact cancer patient survival due to the tumorigenesis ability of surviving cancer cells post-therapy. Efforts are needed to better understand and combat this problem. This study hypothesized that dead cell debris post-radiation therapy creates an advantageous microenvironment rich in metabolic materials promoting the growth of remaining live cancer cells. In this study, live cancer cells are co-cultured with dead cancer cells eradicated by UV radiation to mimic a post-therapy environment. Isotopic labeling metabolomics is used to investigate the metabolic behavior of cancer cells grown in a post-radiation-therapy environment. It is found that post-UV-eradicated dead cancer cells serve as nutritional sources of “off-the-shelf” and precursor metabolites for surviving cancer cells. The surviving cancer cells then take up these metabolites, integrate and upregulate multiple vital metabolic processes, thereby significantly increasing growth in vitro and probably in vivo beyond their intrinsic fast-growing characteristics. Importantly, this active metabolite uptake behavior is only observed in oncogenic but not in non-oncogenic cells, presenting opportunities for therapeutic approaches to interrupt the active uptake process of oncogenic cells without affecting normal cells. The process by which living cancer cells re-use vital metabolites released by dead cancer cells post-therapy is coined in this study as “metabolic recycling” of oncogenic cells.

Original languageEnglish (US)
Article number2200233
JournalAdvanced Biology
Volume7
Issue number2
DOIs
StatePublished - Feb 2023

Keywords

  • C-glucose labeling
  • MYC-transformed lymphoma B cells
  • cancer metabolism
  • glucose metabolism
  • mass spectrometry
  • metabolic recycling
  • metabolomics

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • Biomedical Engineering
  • Biomaterials

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