Severely polarized extracellular acidity around tumour cells.

Autor: Feng Q; Department of Biomedical Engineering, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA.; Department of Pharmacology, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA., Bennett Z; Department of Biomedical Engineering, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA., Grichuk A; Department of Pharmacology, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA.; Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA., Pantoja R; Department of Biomedical Engineering, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA., Huang T; Department of Pharmacology, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA., Faubert B; Children's Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA., Huang G; Department of Biomedical Engineering, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA.; Department of Pharmacology, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA., Chen M; Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA., DeBerardinis RJ; Children's Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.; Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA., Sumer BD; Department of Otolaryngology, University of Texas Southwestern Medical Center, Dallas, TX, USA., Gao J; Department of Biomedical Engineering, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA. jinming.gao@utsouthwestern.edu.; Department of Pharmacology, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA. jinming.gao@utsouthwestern.edu.; Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA. jinming.gao@utsouthwestern.edu.; Department of Otolaryngology, University of Texas Southwestern Medical Center, Dallas, TX, USA. jinming.gao@utsouthwestern.edu.
Jazyk: angličtina
Zdroj: Nature biomedical engineering [Nat Biomed Eng] 2024 Jun; Vol. 8 (6), pp. 787-799. Date of Electronic Publication: 2024 Mar 04.
DOI: 10.1038/s41551-024-01178-7
Abstrakt: Extracellular pH impacts many molecular, cellular and physiological processes, and hence is tightly regulated. Yet, in tumours, dysregulated cancer cell metabolism and poor vascular perfusion cause the tumour microenvironment to become acidic. Here by leveraging fluorescent pH nanoprobes with a transistor-like activation profile at a pH of 5.3, we show that, in cancer cells, hydronium ions are excreted into a small extracellular region. Such severely polarized acidity (pH <5.3) is primarily caused by the directional co-export of protons and lactate, as we show for a diverse panel of cancer cell types via the genetic knockout or inhibition of monocarboxylate transporters, and also via nanoprobe activation in multiple tumour models in mice. We also observed that such spot acidification in ex vivo stained snap-frozen human squamous cell carcinoma tissue correlated with the expression of monocarboxylate transporters and with the exclusion of cytotoxic T cells. Severely spatially polarized tumour acidity could be leveraged for cancer diagnosis and therapy.
(© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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