Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy.
SAFU Department, Regina Elena Cancer Institute, Via Elio Chianesi 51, 00144, Rome, Italy.
Cancer Metastasis Rev. 2019 Jun;38(1-2):93-101. doi: 10.1007/s10555-019-09783-8.
The tumor milieu is characteristically acidic as a consequence of the fermentative metabolism of glucose that results in massive accumulation of lactic acid within the cytoplasm. Tumor cells get rid of excessive protons through exchangers that are responsible for the extracellular acidification that selects cellular clones that are more apt at surviving in this challenging and culling environment. Extracellular vesicles (EVs) are vesicles with diameters ranging from nm to μm that are released from the cells to deliver nucleic acids, proteins, and lipids to adjacent or distant cells. EVs are involved in a plethora of biological events that promote tumor progression including unrestricted proliferation, angiogenesis, migration, local invasion, preparation of the metastatic niche, metastasis, downregulation or hijacking of the immune system, and drug resistance. There is evidence that the release of specific exosomes is increased many folds in cancer patients, as shown by many techniques aimed at evaluating "liquid biopsies". The quality of the exosomal contents has been shown to vary at the different moments of tumor life such as local invasion or metastasis. In vitro studies have recently pointed out that cancer acidity is a major determinant in inducing increased exosome release by human cancer cells, by showing that exosomal release was increased as the pH moved from 7.4 pH to the typical pH of cancer that is 6.5. In this review, we emphasize the recent evidence that tumor acidity and exosomes levels are strictly related and strongly contribute to the malignant tumor phenotypes.
肿瘤微环境通常呈酸性，这是由于葡萄糖的发酵代谢导致细胞质内大量乳酸积累的结果。肿瘤细胞通过负责细胞外酸化的交换器来清除过多的质子，这种酸化选择了更适应这种具有挑战性和淘汰性环境的细胞克隆。细胞外囊泡（EVs）是直径从纳米到微米的囊泡，从细胞中释放出来，将核酸、蛋白质和脂质传递给相邻或远处的细胞。EVs 参与了大量促进肿瘤进展的生物学事件，包括不受限制的增殖、血管生成、迁移、局部侵袭、转移前生态位的准备、转移、下调或劫持免疫系统以及耐药性。有证据表明，癌症患者中特定外泌体的释放增加了许多倍，这可以通过许多旨在评估“液体活检”的技术来证明。已经表明，外泌体内容物的质量在肿瘤生命的不同时刻（如局部侵袭或转移）会发生变化。最近的体外研究表明，癌细胞酸度是诱导人类癌细胞增加外泌体释放的主要决定因素，因为研究表明，随着 pH 从 7.4 pH 向癌症的典型 pH6.5 移动，外泌体释放增加。在这篇综述中，我们强调了最近的证据，即肿瘤酸度和外泌体水平密切相关，并强烈促进了恶性肿瘤表型。
