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Extracellular acidity and increased exosome release as key phenotypes of malignant tumors

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Abstract

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.

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Funding

This work was supported by Regione Lazio FILAS (grant number RU 2014-2041 FascJ9L).

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Authors and Affiliations

  1. Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy

    Mariantonia Logozzi, Davide Mizzoni, Rossella Di Raimo & Stefano Fais

  2. SAFU Department, Regina Elena Cancer Institute, Via Elio Chianesi 51, 00144, Rome, Italy

    Enrico Spugnini

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  1. Mariantonia Logozzi
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  2. Enrico Spugnini
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Logozzi, M., Spugnini, E., Mizzoni, D. et al. Extracellular acidity and increased exosome release as key phenotypes of malignant tumors. Cancer Metastasis Rev 38, 93–101 (2019). https://doi.org/10.1007/s10555-019-09783-8

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