title: Tumour-specific metabolic adaptation to acidosis is coupled to epigenetic stability in osteosarcoma cells.
abstract: The glycolytic-based metabolism of cancers promotes an acidic microenvironment that is responsible for increased aggressiveness. However, the effects of acidosis on tumour metabolism have been almost unexplored. By using capillary electrophoresis with time-of-flight mass spectrometry, we observed a significant metabolic difference associated with glycolysis repression (dihydroxyacetone phosphate), increase of amino acid catabolism (phosphocreatine and glutamate) and urea cycle enhancement (arginino succinic acid) in osteosarcoma (OS) cells compared with normal fibroblasts. Noteworthy, metabolites associated with chromatin modification, like UDP-glucose and N(8)-acetylspermidine, decreased more in OS cells than in fibroblasts. COBRA assay and acetyl-H3 immunoblotting indicated an epigenetic stability in OS cells than in normal cells, and OS cells were more sensitive to an HDAC inhibitor under acidosis than under neutral pH. Since our data suggest that acidosis promotes a metabolic reprogramming that can contribute to the epigenetic maintenance under acidosis only in tumour cells, the acidic microenvironment should be considered for future therapies.
authors.affiliation: Department of Clinical Laboratory Medicine, Shiga University of Medical Science Otsu, Shiga, Japan.
authors.forename: Tokuhiro
authors.initials: T
authors.lastname: Chano
authors.affiliation: Orthopaedic Pathophysiology and Regenerative Medicine Unit, Istituto Ortopedico Rizzoli Bologna, Italy.
authors.forename: Sofia
authors.initials: S
authors.lastname: Avnet
authors.affiliation: Department of Musculoskeletal Oncology, Takai Hospital Tennri, Nara, Japan.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Kusuzaki
authors.affiliation: Orthopaedic Pathophysiology and Regenerative Medicine Unit, Istituto Ortopedico Rizzoli Bologna, Italy.
authors.forename: Gloria
authors.initials: G
authors.lastname: Bonuccelli
authors.affiliation: Institut de Recherche Expérimentale et Clinique (IREC), Pole of Pharmacology (FATH), Université Catholique de Louvain (UCL) Brussels, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: Sonveaux
authors.affiliation: Department of Drug Chemistry and Technologies, Sapienza University of Roma Roma, Italy.
authors.forename: Dante
authors.initials: D
authors.lastname: Rotili
authors.affiliation: Department of Drug Chemistry and Technologies, Sapienza University of RomaRoma, Italy; Pasteur Institute-Cenci Bolognetti Foundation, Sapienza University of RomaRoma, Italy.
authors.forename: Antonello
authors.initials: A
authors.lastname: Mai
authors.affiliation: Orthopaedic Pathophysiology and Regenerative Medicine Unit, Istituto Ortopedico RizzoliBologna, Italy; Department of Biomedical and Neuromotor Sciences, University of BolognaBologna, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Baldini
keywords: Acidosis; epigenome; metabolome; osteosarcoma