Improving the metabolic fidelity of cancer models with a physiological cell culture medium

Vande Voorde, J., Ackermann, T., Pfetzer, N., Sumpton, D., Mackay, G., Kalna, G., Nixon, C., Blyth, K. , Gottlieb, E. and Tardito, S. (2019) Improving the metabolic fidelity of cancer models with a physiological cell culture medium. Science Advances, 5(1), eaau7314. (doi: 10.1126/sciadv.aau7314) (PMID:30613774) (PMCID:PMC6314821)

Abstract

Currently available cell culture media may not reproduce the in vivo metabolic environment of tumors. To demonstrate this, we compared the effects of a new physiological medium, Plasmax, with commercial media. We prove that the disproportionate nutrient composition of commercial media imposes metabolic artifacts on cancer cells. Their supraphysiological concentrations of pyruvate stabilize hypoxia-inducible factor 1α in normoxia, thereby inducing a pseudohypoxic transcriptional program. In addition, their arginine concentrations reverse the urea cycle reaction catalyzed by argininosuccinate lyase, an effect not observed in vivo, and prevented by Plasmax in vitro. The capacity of cancer cells to form colonies in commercial media was impaired by lipid peroxidation and ferroptosis and was rescued by selenium present in Plasmax. Last, an untargeted metabolic comparison revealed that breast cancer spheroids grown in Plasmax approximate the metabolic profile of mammary tumors better. In conclusion, a physiological medium improves the metabolic fidelity and biological relevance of in vitro cancer models.

• Item Type: Articles
• Additional Information: This work was funded by Cancer Research UK (C596/A17196, award 23982).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Tardito, Dr Saverio and Blyth, Professor Karen and Sumpton, Mr David and Nixon, Mr Colin and Pfetzer, Dr Nadja and Gottlieb, Professor Eyal and Mackay, Dr Gillian and Kalna, Dr Gabriela
• Authors: Vande Voorde, J., Ackermann, T., Pfetzer, N., Sumpton, D., Mackay, G., Kalna, G., Nixon, C., Blyth, K., Gottlieb, E., and Tardito, S.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences; College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
• Journal Name: Science Advances
• Publisher: American Association for the Advancement of Science
• ISSN: 2375-2548
• ISSN (Online): 2375-2548
• Published Online: 02 January 2019
• Copyright Holders: Copyright © 2019 The Authors
• First Published: First published in Science Advances 5(1): eaau7314
• Publisher Policy: Reproduced under a Creative Commons License