Cancer-associated cells release citrate to support tumour metastatic progression
Drexler K, Schmidt KM, Jordan K, Federlin M, Milenkovic VM, Liebisch G, Artati A, Schmidl C, Madej G, Tokarz J, Cecil A, Jagla W, Härteis S, Aung T, Wagner C, Kolodziejczyk M, Heinke S, Stanton EH, Schwertner B, Riegel D, Wetzel CH, Buchalla W, Proescholdt M, Klein CA, Berneburg M, Schlitt HJ, Brabletz T, Ziegler C, Parkinson EK, Gaumann A, Geissler EK, Adamski J, Haferkamp S, Mycielska ME (2021)
Publication Type: Journal article
Publication year: 2021
Journal
Book Volume: 4
Journal Issue: 6
Abstract
Citrate is important for lipid synthesis and epigenetic regulation in addition to ATP production. We have previously reported that cancer cells import extracellular citrate via the pmCiC transporter to support their metabolism. Here, we show for the first time that citrate is supplied to cancer by cancer-associated stroma (CAS) and also that citrate synthesis and release is one of the latter's major metabolic tasks. Citrate release from CAS is controlled by cancer cells through cross-cellular communication. The availability of citrate from CAS regulated the cytokine profile, metabolism and features of cellular invasion. Moreover, citrate released by CAS is involved in inducing cancer progression especially enhancing invasiveness and organ colonisation. In line with the in vitro observations, we show that depriving cancer cells of citrate using gluconate, a specific inhibitor of pmCiC, significantly reduced the growth and metastatic spread of human pancreatic cancer cells in vivo and muted stromal activation and angiogenesis. We conclude that citrate is supplied to tumour cells by CAS and citrate uptake plays a significant role in cancer metastatic progression.
Authors with CRIS profile
Silke Härteis
Thomas Brabletz Lehrstuhl für Experimentelle Medizin mit dem Schwerpunkt Molekulare Pathogeneseforschung
Thomas Brabletz Lehrstuhl für Experimentelle Medizin mit dem Schwerpunkt Molekulare Pathogeneseforschung
Involved external institutions
Universitätsklinikum Regensburg
Germany (DE)
Universität Regensburg
Germany (DE)
Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich
Germany (DE)
Regensburg Center for Interventional Immunology
Germany (DE)
Queen Mary University of London
United Kingdom (GB)
Germany (DE)
Universität Regensburg
Germany (DE)
Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich
Germany (DE)
Regensburg Center for Interventional Immunology
Germany (DE)
Queen Mary University of London
United Kingdom (GB)
How to cite
APA:
Drexler, K., Schmidt, K.M., Jordan, K., Federlin, M., Milenkovic, V.M., Liebisch, G.,... Mycielska, M.E. (2021). Cancer-associated cells release citrate to support tumour metastatic progression. Life Science Alliance, 4(6). https://doi.org/10.26508/lsa.202000903
MLA:
Drexler, Konstantin, et al. "Cancer-associated cells release citrate to support tumour metastatic progression." Life Science Alliance 4.6 (2021).
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