The Relationship between tumor blood flow, angiogenesis, tumor hypoxia, and aerobic glycolysis

Thursday, 23/01/2014  |   Uncategorized  |  no comments


Anaerobic glycolysis is the transformation of glucose to pyruvate when limited amounts of oxygen (O2) are available. persistent metabolism of glucose to lactate even in aerobic conditions is an adaptation to intermittent hypoxia in pre-malignant lesions. However, upregulation of glycolysis leads to microenvironmental acidosis requiring evolution to phenotypes resistant to acid-induced cell toxicity.

The survival of cancer cells is contingent on their supply of oxygen and nutrients such as glucose via the bloodstream. The establishment and growth of malignant tumors are, therefore, critically dependent on their ability to stimulate the formation of new blood vessels (angiogenesis) to support their metabolic needs

Antiangiogenic therapies are being pursued as a means of starving tumors of their energy supply. Although numerous studies show that such therapies render tumors hypoxic, just as many studies have, surprisingly, shown improved tumor oxygenation. These contradicting findings challenge both the original rationale for antiangiogenic therapy and our understanding of the physiology of tissue oxygenation. The flow–diffusion equation, which describes the relation between blood flow and the extraction of freely diffusible molecules in tissue, was recently extended to take the heterogeneity of capillary transit times (CTH) into account. CTH is likely to be high in the chaotic microvasculature of a tumor, increasing the effective shunting of blood through its capillary bed. We review the properties of the extended flow–diffusion equation in tumor tissue. Elevated CTH reduces the extraction of oxygen, glucose, and cytotoxic molecules. The extent to which their net extraction is improved by antiangiogenic therapy, in turn, depends on the extent to which CTH is normalized by the treatment. The extraction of oxygen and glucose are affected to different extents by elevated CTH, and the degree of aerobic glycolysis—known as the Warburg effect—is thus predicted to represent an adaptation to the CTH of the local microvasculature.


Østergaard L, Tietze A, Nielsen T, et al. Cancer Res September 15, 2013 73; 5618. doi: 10.1158/0008-5472.CAN-13-0964



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