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Contribution of pH Alterations to the Tumor Microenvironment

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Book cover Tumor Cell Metabolism

Abstract

A common feature of solid tumors is the accumulation of protons within the extracellular environment, which coupled with disorganized vasculature and inefficient perfusion and clearance cause tumors being acidic tissues. Tumor acidosis, historically associated with increased glycolytic rates but now also explained by the overall high metabolic rates of proliferating cancer cells, represents an important determinant of malignant progression. Low pH in tumors and the reversed gradient between intra- and extracellular pH are associated with increased invasion and metastasis, resistance to cell death and apoptosis, resistance to chemo- and radiotherapy, increased angiogenesis, and escape from immune control. The acidic conditions created within the tumor microenvironment may represent a selection force for more aggressive cancer cells and at the same time a toxic environment for stromal cells. In this chapter, we will summarize the current knowledge about mechanistic determinants and pathophysiological effects of tumor acidosis.

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Acknowledgments

Angela Strambi was supported by the Boncompagni-Ludovisi Foundation. Angelo De Milito is supported by grants from the Association for International Cancer Research (grant #11-0522) and the Swedish Cancer Society (grant # CAN 2012/415).

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  1. Department of Oncology-Pathology, Cancer Center Karolinska, R8:00, Karolinska Institute, Stockholm, Sweden

    Angela Strambi & Angelo De Milito

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Correspondence to Angelo De Milito .

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  1. Inst. of Veterinary Physiology and Bioch, Justus-Liebig-University of Giessen, Gießen, Hessen, Germany

    Sybille Mazurek

  2. Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden

    Maria Shoshan

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Strambi, A., De Milito, A. (2015). Contribution of pH Alterations to the Tumor Microenvironment. In: Mazurek, S., Shoshan, M. (eds) Tumor Cell Metabolism. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1824-5_9

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