Intra- and Extracellular pH in Solid Tumors

  • Chang W. Song
  • HeonJoo Park
  • Brian D. Ross
Part of the Cancer Drug Discovery and Development book series (CDD&D)


It has long been known that the interstitial environment in malignant tumors is acidic as a result of accumulation of lactic acid and other acidic metabolites. Neoplastic cells metabolize glucose preferentially through glycolysis, even in an aerobic environment resulting in the production of lactic acid (1). In solid tumors, the supply of oxygen is limited because of sluggish blood perfusion through a heterogeneously distributed vascular network, resulting in diffusion-limited hypoxia (2–5). Furthermore, it has been observed that blood perfusion through capillary-like tumor vessels often slows down, stops, or even completely reverses its direction, creating perfusion-limited hypoxia (5,6). Under such hypoxic conditions, cells metabolize glucose through anaerobic glycolysis and produce lactic acid (1, 7–9). Furthermore, a sudden induction of hypoxic condition caused by sudden cessation of blood perfusion may cause hydrolysis of ATP, resulting in the generation of H+ ions (10). For reasons unknown, small amounts of β-hydrobutyric acid were detected in experimental tumors (9). Such overproduction of acidic metabolites, notably lactic acid combined with slow discharge of the acidic metabolites via sluggish tumor blood flow, results in accumulation of acidic metabolites in the tumors. The acidic interstitial or extracellular environment in tumors inevitably influences the intracellular acidity, which in turn would exert a marked influence on the proliferation of parenchyma and endothelial cells. This chapter discusses the relationship between the extracellular and intracellular acidity in tumors, the influence of the intracellular acidity on angiogenesis, and of that on the response of tumor cells to various antineoplastic regimens.


Acidic Environment Blood Perfusion Acidic Metabolite Intracellular Environment Intracellular Acidity 
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© Springer Science+Business Media New York 1999

Authors and Affiliations

  • Chang W. Song
  • HeonJoo Park
  • Brian D. Ross

There are no affiliations available

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