The role of HIF prolyl hydroxylases in tumor progression and metastasis

• Applicant: Professor Dr. Georg Breier
• Subject Area: Pathology
• Term: from 2006 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 22095729

Hypoxia is a major driving force for tumor vascularization and progression. In mammalian cells, the transcriptional complex, hypoxia-inducuble factor (HIF), has emerged as a key regulator of physiological and pathological processes, mediating both local and systemic responses to hypoxia. HIF activity and stability, in turn, is tightly controlled through the enzymatic activity of prolyl and asparaginyl hydroxylases which serve as cellular oxygen sensors. While the role of HIF in activating the angiogenic program in tumor cells is well established, little is known about the role of hypoxia signalling in endothelial cells. Recent evidence suggests that HIF activity in endothelial cells is critical for angiogenesis and tumor progression. In this project, therefore, we want to focus on the influence of endothelial HIF hydroxylases on the vascularization, growth and metastasis of experimental tumors in mice. The activity of HIF hydroxylases will be modulated in tumor endothelial cells as well as in tumor cells by gain-of-function and loss-of-function experiments, both through virus-mediated gene transfer and transgenesis in mice. These studies will eventually lead to a better understanding of the interplay between tumor cells and the vasculature and may therefore be helpful in the development of new therapies.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1190: The Tumour-Vessel Interface
• Participating Person: Professor Ben Wielockx, Ph.D.