细胞外
细胞内pH值
癌细胞
细胞毒性T细胞
肿瘤微环境
化学
运输机
生物物理学
癌症
细胞生物学
癌症研究
生物化学
生物
体外
肿瘤细胞
基因
遗传学
作者
Qiang Feng,Zachary T. Bennett,Anthony Grichuk,Raymundo Pantoja,Tongyi Huang,Brandon Faubert,Gang Huang,Mingyi Chen,Ralph J. DeBerardinis,Baran D. Sumer,Jinming Gao
标识
DOI:10.1038/s41551-024-01178-7
摘要
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.
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