Mechanisms Underlying Hypoxia Development in Tumors

Abstract

The purpose of this review is to critically evaluate physiologic mechanisms that lead to hypoxia in tumors. This review will challenge some of the current paradigms and present an alternative view. There are two types of hypoxia, as described radiobiologically. Long intercapillary distances between microvessels are believed to be causal fordiffusion limited or chronic hypoxia.Intermittent vascular stasis is commonly believed to be responsiblefor perfusion limited or acute hypoxia.If one considers the multitude of factors that could influence oxygen transport, it becomes clear that these two classifications are gross oversimplifications of a more complex process. Factors that are known to affect delivery include microvessel density, vessel orientation, red cell flux, hemoglobin saturation and blood viscosity, to name a few. One must also consider the oxygen consumption rate, which can be influenced by cell proliferation rate and other factors, such as inflammation. This review will present a comprehensive model including factors governing oxygen transport in tumors that provides a testable mechanistic underpinning for future research on this subject. The increased interest in tumor hypoxia because of its influences on gene expression and selection for more aggressive phenotype further emphasizes the need for more detailed study.