Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: a review.

TLDR

Significant variations in blood flow, oxygen, and nutrient supply parameters are expected within and between tumors of the same grade and stage. This review aims to summarize current knowledge of blood flow and perfusion parameters that define the metabolic microenvironment of human tumors and to identify key pathophysiological factors for future research to tailor treatment protocols and predict therapeutic response. The authors compile literature data on blood flow, oxygen, nutrient supply, and tissue oxygen/pH distribution in human tumors, comparing them with normal tissues and animal models where possible. Experimental evidence indicates many human tumors have compromised, anisotropic blood supply, resulting in oxygen‑depleted, nutrient‑deprived, and acidic microenvironments.

Abstract

The objective of this review article is to summarize current knowledge of blood flow and perfusion-related parameters, which usually go hand in hand and in turn define the cellular metabolic microenvironment of human malignancies. A compilation of available data from the literature on blood flow, oxygen and nutrient supply, and tissue oxygen and pH distribution in human tumors is presented. Whenever possible, data obtained for human tumors are compared with the respective parameters in normal tissues, isotransplanted or spontaneous rodent tumors, and xenografted human tumors. Although data on human tumors in situ are scarce and there may be significant errors associated with the techniques used for measurements, experimental evidence is provided for the existence of a compromised and anisotropic blood supply to many tumors. As a result, O2-depleted areas develop in human malignancies which coincide with nutrient and energy deprivation and with a hostile metabolic microenvironment (e.g., existence of severe tissue acidosis). Significant variations in these relevant parameters must be expected between different locations within the same tumor, at the same location at different times, and between individual tumors of the same grading and staging. Furthermore, this synopsis will attempt to identify relevant pathophysiological parameters and other related areas future research of which might be most beneficial for designing individually tailored treatment protocols with the goal of predicting the acute and/or long-term response of tumors to therapy.