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Extracellular acidity, a “reappreciated” trait of tumor environment driving malignancy: perspectives in diagnosis and therapy

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Abstract

Tumors are ecosystems which develop from stem cells endowed with unlimited self-renewal capability and genetic instability, under the effects of mutagenesis and natural selection imposed by environmental changes. Abnormal vascularization, reduced lymphatic network, uncontrolled cell growth frequently associated with hypoxia, and extracellular accumulation of glucose metabolites even in the presence of an adequate oxygen level are all factors contributing to reduce pH in the extracellular space of tumors. Evidence is accumulating that acidity is associated with a poor prognosis and participates actively to tumor progression. This review addresses some of the most experimental evidences providing that acidity of tumor environment facilitates local invasiveness and metastatic dissemination, independently from hypoxia, with which acidity is often but not always associated. Clinical investigations have also shown that tumors with acidic environment are associated with resistance to chemotherapy and radiation-induced apoptosis, suppression of cytotoxic lymphocytes, and natural killer cells tumoricidal activity. Therefore, new technologies for functional and molecular imaging as well as strategies directed to target low extracellular pH and low pH-adapted tumor cells might represent important issues in oncology.

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Acknowledgments

We acknowledge the “Istituto Toscano Tumori” and Ente Cassa di Risparmio di Firenze for their financial support.

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The authors declare that they have no conflict of interest.

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  1. Department of Experimental and Clinical Biomedical Sciences, Section of Experimental Pathology and Oncology, University of Florence, Viale G.B. Morgagni, 50, 50134, Florence, Italy

    Silvia Peppicelli, Francesca Bianchini & Lido Calorini

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  1. Silvia Peppicelli
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  2. Francesca Bianchini
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  3. Lido Calorini
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Peppicelli, S., Bianchini, F. & Calorini, L. Extracellular acidity, a “reappreciated” trait of tumor environment driving malignancy: perspectives in diagnosis and therapy. Cancer Metastasis Rev 33, 823–832 (2014). https://doi.org/10.1007/s10555-014-9506-4

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