Department of Cancer Physiology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Avenue, Tampa, FL, 33612, USA.
Department of Oncological Sciences, University of South Florida, Tampa, FL, USA.
Cancer Metastasis Rev. 2019 Jun;38(1-2):149-155. doi: 10.1007/s10555-019-09787-4.
The extracellular pH of solid tumors is unequivocally acidic due to a combination of high rates of lactic acid production (a consequence of fermentative glycolytic metabolism) and poor perfusion. This has been documented by us and others in a wide variety of solid tumor models, primarily using magnetic resonance spectroscopic imaging (MRSI). This acidity contributes to tumor progression by inducing genome instability, promoting local invasion and metastases, inhibiting anti-tumor immunity, and conferring resistance to chemo- and radio-therapies. Systemic buffer therapies can neutralize tumor acidity and has been shown to inhibit local invasion and metastasis and improve immune surveillance in a variety of cancer model systems. This review will revisit the causes and consequences of acidosis by summarizing strategies used by cancer cells to adapt to acidosis, and how this acidity associated with carcinogenesis, metastasis, and immune function. Finally, this review will discuss how neutralization of acidity can be used to inhibit carcinogenesis and metastasis and improve anti-cancer immunotherapy.
由于乳酸生成率高（发酵糖酵解代谢的结果）和灌注不良，实体瘤的细胞外 pH 值无疑呈酸性。这一点已被我们和其他人在广泛的实体瘤模型中所证实，主要使用磁共振波谱成像（MRSI）。这种酸度通过诱导基因组不稳定性、促进局部侵袭和转移、抑制抗肿瘤免疫以及赋予化疗和放疗耐药性来促进肿瘤进展。全身缓冲治疗可以中和肿瘤酸度，并已被证明可以抑制局部侵袭和转移，并改善各种癌症模型系统中的免疫监测。本综述将通过总结癌细胞适应酸中毒的策略，以及这种与致癌、转移和免疫功能相关的酸度，重新审视酸中毒的原因和后果。最后，本综述将讨论如何中和酸度以抑制致癌和转移并改善抗癌免疫治疗。
