Expression of HIF-1alpha and GLUT-1 in human xenograft tumors in immundeficient mice

Abstract

For the treatment of solid malignant tumors measuring tumor hypoxia would be clinically desirable as hypoxia influences the resistance of a solid malignant tumor with regard to chemo- and radiotherapy. The transcriptional factor HIF-1α plays a fundamental role in adaption of tissue to hypoxic conditions. It plays a crucial role for the survival of tissue under these conditions and coordinates the adaption to these circumstances by regulation of cell proliferation, angiogenesis, metabolic changes and many other factors as well. GLUT-1 a target gene of the transcriptional factor HIF-1α is discussed as endogenous hypoxia marker but its suitability is disputed up to now. We investigated different tumor entities for a correlation in expression of HIF-1α and GLUT-1 expression in order to investigate if there is a correlation of HIF-1α and GLUT-1 expression. A series of archived primary human xenograft tumors grown in immunodeficient mice were analyzed for the correlation of the expression of HIF-1α and GLUT-1 by using immunohistochemistry. The comparison of both revealed no correlation in HIF-1α and GLUT-1 expression throughout different tumor entities. HIF-1α expression showed two different distribution pattern, pattern I and II. Pattern II shows an increase in staining intensity of HIF-1α in dependence to blood vessel distance and GLUT-1 expression in a marginal zone at the border to necrosis and in necrosis itself. In pattern I a nearly constant HIF-1α expression throughout the whole vital tumor cell nuclei without an influence of supplying blood vessels and without any significant GLUT-1 expression can be observed. Another difference exists in the expression of HIF-Iα. In type A the HIF-1α expression intensity is increasing correspondent to blood vessel distance and in type B consistent staining intensity can be observed throughout all vital tumor cells without any or only small influence by blood vessels. As the distribution of HIF-1α and GLUT-1 does not match in vivo there is no clear connection between the central mediator in adaption to hypoxia HIF-1α and its target gene GLUT-1. Hence GLUT-1 cannot serve as an as endogenous hypoxia marker.