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

Voorde, Johan Vande; Ackermann, Tobias; Pfetzer, Nadja; Sumpton, David; Mackay, Gillian; Kalna, Gabriela; Nixon, Colin; Blyth, Karen; Gottlieb, Eyal; Tardito, Saverio

doi:10.1126/sciadv.aau7314

Cited by 291 publications

(308 citation statements)

References 24 publications

Supporting

Mentioning

259

Contrasting

Order By: Relevance

“…The lack of investigations is most likely due to their absence in tissue culture medium, despite being present at often significant concentrations in tissues, plasma and cerebrospinal fluid. Indeed, both the recently described plasma-like culture media contain many of these metabolites, 78,79 indicative of an increasing awareness that our common culture systems do not adequately address many aspects of cancer cell biology, forcing the metabolic network into an aberrantly small space and reducing our ability to efficiently translate novel agents to target cancer metabolism into patients.…”

Section: Non-proteinogenic Amino Acids In Cancer Metabolismmentioning

confidence: 99%

New aspects of amino acid metabolism in cancer

2019

View full text Add to dashboard Cite

An abundant supply of amino acids is important for cancers to sustain their proliferative drive. Alongside their direct role as substrates for protein synthesis, they can have roles in energy generation, driving the synthesis of nucleosides and maintenance of cellular redox homoeostasis. As cancer cells exist within a complex and often nutrient-poor microenvironment, they sometimes exist as part of a metabolic community, forming relationships that can be both symbiotic and parasitic. Indeed, this is particularly evident in cancers that are auxotrophic for particular amino acids. This review discusses the stromal/cancer cell relationship, by using examples to illustrate a number of different ways in which cancer cells can rely on and contribute to their microenvironmentboth as a stable network and in response to therapy. In addition, it examines situations when amino acid synthesis is driven through metabolic coupling to other reactions, and synthesis is in excess of the cancer cell's proliferative demand. Finally, it highlights the understudied area of non-proteinogenic amino acids in cancer metabolism and their potential role.

show abstract

Section: Non-proteinogenic Amino Acids In Cancer Metabolismmentioning

confidence: 99%

New aspects of amino acid metabolism in cancer

2019

View full text Add to dashboard Cite

show abstract

“…We cultured all the cell lines in ambient oxygen conditions in conventional, commercial media with a non-physiological nutrient composition. A few recent studies have emphasized the significant metabolic impact of media formulated to mimic physiological conditions (Cantor et al, 2017; Vande Voorde et al, 2019). We used conventional culture conditions so that we could integrate metabolic phenotyping with orthogonal datasets (transcriptional, proteomic and therapeutic profiling), all of which were obtained under these same conditions.…”

Section: Discussionmentioning

confidence: 99%

Metabolic Diversity in Human Non-Small Cell Lung Cancer Cells

Chen

Cai

Huffman

et al. 2019

Preprint

View full text Add to dashboard Cite

SummaryIntermediary metabolism in cancer cells is regulated by diverse cell-autonomous processes including signal transduction and gene expression patterns arising from specific oncogenotypes and cell lineages. Although it is well established that metabolic reprogramming is a hallmark of cancer, we lack a full view of the diversity of metabolic programs in cancer cells and an unbiased assessment of the associations between metabolic pathway preferences and other cell-autonomous processes. Here we quantified over 100 metabolic features, mostly from 13C enrichment of molecules from central carbon metabolism, in over 80 non-small cell lung cancer (NSCLC) cell lines cultured under identical conditions. Because these cell lines were extensively annotated for oncogenotype, gene expression, protein expression and therapeutic sensitivity, the resulting database enables the user to uncover new relationships between metabolism and these orthogonal processes.

show abstract

“…Further investigation is required as pABA is the only known metabolite present in adult human plasma at variable concentrations (0.15 -6.56 µM) 26 and increasing folate supplementation in malaria endemic areas 27 has the potential to result in an increased risk of infection and failure of antifolate treatments. It is worth mentioning that all metabolites except pABA are present in the CM at supraphysiological concentrations 28 .…”

Section: Development Of P Falciparum Asexual and Gametocyte Stages Imentioning

confidence: 98%

Metabolic dependency of chorismate in Plasmodium falciparum

Valenciano

Fernández-Murga

Merino

et al. 2019

Preprint

View full text Add to dashboard Cite

The shikimate pathway, a metabolic pathway absent in humans, is responsible for the production of chorismate, a branch point metabolite. In the malaria parasite, chorismate is postulated to be a direct precursor in the synthesis of p-aminobenzoic acid (folate biosynthesis), p-hydroxybenzoic acid (ubiquinone biosynthesis), menaquinone, and aromatic amino acids. While the potential value of the shikimate pathway as a drug target is debatable, the metabolic dependency of chorismate in P. falciparum remains unclear. Current evidence suggests that the main role of chorismate is folate biosynthesis despite ubiquinone biosynthesis being active and essential in the malaria parasite. Our goal in the present work was to expand our knowledge of the ubiquinone head group biosynthesis and its potential metabolic dependency on chorismate in P. falciparum. These data led us to further characterize the mechanism of action of MMV688345, a compound from the open-access "Pathogen Box" collection from Medicine for Malaria Venture. We systematically assessed the development of both asexual and sexual stages of P. falciparum in a defined medium in the absence of an exogenous supply of chorismate end-products and present biochemical evidence suggesting that the benzoquinone ring of ubiquinones in this parasite may be synthesized through a yet unidentified route.Human malaria accounts for more than 400,000 deaths every year, with Plasmodium falciparum being the deadliest of the species that infects humans 1 . All Plasmodium species have a complex life cycle that occurs between the human host and the Anopheles mosquito vector. Clinical symptoms are caused by the asexual intraerythrocytic cycle of the parasite that lasts around 48 h in P. falciparum. During the asexual cycle, the parasite progresses through four morphologically different stages: ring, trophozoite, and schizont stages, ending with the release of merozoites that will invade new erythrocytes. A small percentage (0.1-0.2) of parasites commit to gametocytogenesis (sexual development) during the asexual cycle and mature female and male gametocytes are transmitted to a female mosquito when it feeds on an infected human. Gametocytes are asymptomatic, non-replicating forms that can persist for weeks in circulating blood. In contrast to other species of Plasmodium, P. falciparum gametocytes develop through five (I to V) morphologically distinct stages, taking 10 to 12 days to fully mature into stage V gametocytes.Artemisinin Combination Therapies (ATCs) are the frontline treatment for malaria, however, resistance to artemisinin has been confirmed and is increasing in prevalence 2 . Thus, there is an urgent need

show abstract

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

Abstract: Plasmax, a physiological cell culture medium, prevents metabolic artifacts imposed on cancer cells by commonly used media.

Cited by 291 publications

References 24 publications

New aspects of amino acid metabolism in cancer

New aspects of amino acid metabolism in cancer

Metabolic Diversity in Human Non-Small Cell Lung Cancer Cells

Metabolic dependency of chorismate in Plasmodium falciparum

Contact Info

Product

Resources

About