Drexler, Konstantin and Schmidt, Katharina M. and Jordan, Katrin and Federlin, Marianne and Milenkovic, Vladimir M. and Liebisch, Gerhard and Artati, Anna and Schmidl, Christian and Madej, Gregor and Tokarz, Janina and Cecil, Alexander and Jagla, Wolfgang and Haerteis, Silke and Aung, Thiha and Wagner, Christine and Kolodziejczyk, Maria and Heinke, Stefanie and Stanton, Evan H. and Schwertner, Barbara and Riegel, Dania and Wetzel, Christian H. and Buchalla, Wolfgang and Proescholdt, Martin and Klein, Christoph A. and Berneburg, Mark and Schlitt, Hans J. and Brabletz, Thomas and Ziegler, Christine and Parkinson, Eric K. and Gaumann, Andreas and Geissler, Edward K. and Adamski, Jerzy and Haferkamp, Sebastian and Mycielska, Maria E. (2021) Cancer-associated cells release citrate to support tumour metastatic progression. LIFE SCIENCE ALLIANCE, 4 (6): e202000903. ISSN 2575-1077
Full text not available from this repository. (Request a copy)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 theirmetabolism. Here, we showfor thefirst time that citrate is supplied to cancer by cancer-associated stroma (CAS) and also that citrate synthesis and release is one of the latter'smajormetabolic 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.
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