Metabolic Recycling Enhances Proliferation in MYC-Transformed Lymphoma B Cells

Authors

Cissy Zhang, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Giang Hoang, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Nabeel Attarwala, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.Follow
Arthur J. Cooper, Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY, 10595, USA.Follow
Ryoichi Asaka, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.Follow
Anne Le, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.

Author Type(s)

Faculty

DOI

10.1002/adbi.202200233

Journal Title

Advanced Biology

First Page

e2200233

Document Type

Article

Publication Date

2-1-2023

Department

Biochemistry and Molecular Biology

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.

Recommended Citation

Zhang, C., Hoang, G., Attarwala, N., Cooper, A. J., Asaka, R., & Le, A. (2023). Metabolic Recycling Enhances Proliferation in MYC-Transformed Lymphoma B Cells. Advanced Biology, 7 (2), e2200233. https://doi.org/10.1002/adbi.202200233