Cancer-associated cells release citrate to support tumour metastatic progression.

Autor:	Drexler K; Department of Dermatology, University Medical Centre, Regensburg, Germany., Schmidt KM; Department of Surgery, University Medical Center, Regensburg, Germany., Jordan K; Department of Surgery, University Medical Center, Regensburg, Germany., Federlin M; Department of Conservative Dentistry and Periodontology, University Medical Center, Regensburg, Germany., Milenkovic VM; Department of Psychiatry and Psychotherapy, University of Regensburg, Regensburg, Germany., Liebisch G; Institute of Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, Regensburg, Germany., Artati A; Research Unit Molecular Endocrinology and Metabolism, Helmholtz Zentrum München, German Research Centre for Environmental Health, Neuherberg, Germany., Schmidl C; Regensburg Center for Interventional Immunology, Regensburg, Germany., Madej G; Department of Structural Biology, Institute of Biophysics and Physical Biochemistry, University of Regensburg, Regensburg, Germany., Tokarz J; Research Unit Molecular Endocrinology and Metabolism, Helmholtz Zentrum München, German Research Centre for Environmental Health, Neuherberg, Germany., Cecil A; Research Unit Molecular Endocrinology and Metabolism, Helmholtz Zentrum München, German Research Centre for Environmental Health, Neuherberg, Germany., Jagla W; Institute of Pathology, Kaufbeuren-Ravensburg, Kaufbeuren, Germany., Haerteis S; Institute for Molecular and Cellular Anatomy, University of Regensburg, Regensburg, Germany., Aung T; Institute for Molecular and Cellular Anatomy, University of Regensburg, Regensburg, Germany.; Center of Plastic, Aesthetic, Hand and Reconstructive Surgery, University of Regensburg, Regensburg, Germany., Wagner C; Department of Surgery, University Medical Center, Regensburg, Germany., Kolodziejczyk M; Department of Surgery, University Medical Center, Regensburg, Germany., Heinke S; Department of Surgery, University Medical Center, Regensburg, Germany., Stanton EH; Department of Surgery, University Medical Center, Regensburg, Germany., Schwertner B; Department of Dermatology, University Medical Centre, Regensburg, Germany., Riegel D; Regensburg Center for Interventional Immunology, Regensburg, Germany., Wetzel CH; Department of Psychiatry and Psychotherapy, University of Regensburg, Regensburg, Germany., Buchalla W; Department of Conservative Dentistry and Periodontology, University Medical Center, Regensburg, Germany., Proescholdt M; Department of Neurosurgery, University Hospital Regensburg, Regensburg, Germany., Klein CA; Experimental Medicine and Therapy Research, University of Regensburg, Regensburg, Germany., Berneburg M; Department of Dermatology, University Medical Centre, Regensburg, Germany., Schlitt HJ; Department of Surgery, University Medical Center, Regensburg, Germany., Brabletz T; Department of Experimental Medicine 1, Friedrich-Alexander-University Erlangen, Erlangen, Germany., Ziegler C; Department of Structural Biology, Institute of Biophysics and Physical Biochemistry, University of Regensburg, Regensburg, Germany., Parkinson EK; Centre for Immunobiology and Regenerative Medicine, Blizard Institute, Barts and The London School of Medicine and Dentistry, London, UK., Gaumann A; Institute of Pathology, Kaufbeuren-Ravensburg, Kaufbeuren, Germany., Geissler EK; Department of Surgery, University Medical Center, Regensburg, Germany., Adamski J; Research Unit Molecular Endocrinology and Metabolism, Helmholtz Zentrum München, German Research Centre for Environmental Health, Neuherberg, Germany.; Lehrstuhl für Experimentelle Genetik, Technische Universität München, Munich, Germany.; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore., Haferkamp S; Department of Dermatology, University Medical Centre, Regensburg, Germany sebastian.haferkamp@ukr.de., Mycielska ME; Department of Surgery, University Medical Center, Regensburg, Germany maria.mycielska@ukr.de.
Jazyk:	angličtina
Zdroj:	Life science alliance [Life Sci Alliance] 2021 Mar 23; Vol. 4 (6). Date of Electronic Publication: 2021 Mar 23 (Print Publication: 2021).
DOI:	10.26508/lsa.202000903
Abstrakt:	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. (© 2021 Drexler et al.)
Databáze:	MEDLINE
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