Cancer-associated cells release citrate to support tumour metastatic progression

• DOI: 10.26508/lsa.202000903
• Publication Date: 2021-03-23T20:10:29Z
• Authors: Konstantin Drexler; Katharina M Schmidt; Katrin Jordan; Marianne Federlin; Vladimir M Milenk...; Gerhard Liebisch; Anna Artati; Christian Schmidl; Gregor Madej; Janina Tokarz; Alexander Cecil; Wolfgang Jagla; Silke Haerteis; Thiha Aung; Christine Wagner; Maria Kolodziejczyk; Stefanie Heinke; Evan H Stanton; Barbara Schwertner; Dania Riegel; Christian H Wetzel; Wolfgang Buchalla; Martin Proescholdt; Christoph A Klein; Mark Berneburg; Hans J Schlitt; Thomas Brabletz; Christine Ziegler; Eric K Parkinson; Andreas Gaumann; Edward K Geissler; Jerzy Adamski; Sebastian Haferkamp; Maria E Mycielska
• Keywords: 0301 basic medicine; 570; ddc:610; 610 Medizin; 610; Citric Acid; ddc:; Epigenesis, Genetic; 3. Good health; Pancreatic Neoplasms; 03 medical and health sciences; Cancer-Associated Fibroblasts; Cell Line, Tumor; Tumor Microenvironment; Humans; Neoplasm Metastasis; Stromal Cells; Research Articles

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 support their metabolism. Here, we show first time supplied by cancer-associated stroma (CAS) also release one of latter’s major metabolic tasks. from CAS controlled through cross-cellular communication. The availability regulated cytokine profile, metabolism features cellular invasion. Moreover, released involved inducing progression especially enhancing invasiveness organ colonisation. In line with vitro observations, depriving using gluconate, a specific inhibitor pmCiC, significantly reduced growth metastatic spread human pancreatic vivo muted stromal activation angiogenesis. conclude tumour uptake plays significant role progression.