Severely polarized extracellular acidity around tumour cells.
Nat Biomed Eng
; 8(6): 787-799, 2024 Jun.
Article
em En
| MEDLINE
| ID: mdl-38438799
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transportadores de Ácidos Monocarboxílicos
/
Microambiente Tumoral
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Biomed Eng
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos