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Scientists define a new mechanism leading to tumor hypoxia
Date:5/9/2013

p>The researchers used a 9L glioma model with defined and ordered vascular flow originating from the rat epigastric artery and vein pair to study hypoxia distribution using both immuno-histochemical and MRI methodologies. They further developed a gamma-H2AX labeling technique for defining hypoxia impact on DNA damage. Macroscopic regions of hypoxia occurred in every fourth of examined tumors. The researchers found large (mm) regions of moderate (0.3%) hypoxia that were not easily explained by the existing concepts of diffusion or perfusion-limited hypoxia. Due to its stability and the fact that it occurs over a large scale, this mechanism for the distribution of oxygen and other nutrients and drugs has substantial implications for hypoxia imaging, hypoxic cell targeting and for therapy effectiveness.

Hypoxia has historically been seen as occurring as the result of events at a microscopic scale. Diffusion-limited hypoxia, described in the 1950s by Thomlinson and Gray is stable and occurs as a gradient at distances of 100-200uM from vessels. Transient or perfusion limited hypoxia was described more recently and added to the complexity of detecting and targeting hypoxic cells, as well as having biological implications for tumor cell resistance to therapy. The current report superimposes a larger scale, presumably stable hypoxic gradient over these two mechanisms and could impact the interpretation of studies on hypoxia biology, approaches to hypoxia detection and targeting.

Hypoxia is a negative prognostic indicator for radiotherapy, chemotherapy and surgery and also predicts for an aggressive and metastatic phenotype. Understanding its causes can aid in detection and intervention of cancer.


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