The influence of the extracellular RNA/RNase system on humoral and cellular reactions at the tumor-vessel interface

• Applicant: Professor Dr. Klaus T. Preissner
• Subject Area: Pathology
• Term: from 2006 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 21994415

The tumor-vessel interface constitutes a fragile interaction system that is associated with continuous tissue remodelling including cell invasion, proliferation and apoptosis, regulated by humoral and cellular mediators. Tumor burden in patients has been correlated with a hypercoagulable state and thromboembolic complications, yet, any insights into causal relations or molecular mechanisms are missing. We have recently identified extracellular RNA (eRNA) as a novel procoagulant cofactor for serine proteases and eRNA promotes the initiation and progression of blood coagulation in vivo. On the other hand RNase administration had a potent antithrombotic effect in animal models of thrombosis. Moreover, both natural and artificial eRNA lead to activation of endothelial cells. Based on these findings we hypothesize that eRNA plays an important but yet unrecognized role in humoral and cellular activities within the tumor-vessel interface. In this project we aim to: (a) characterize eRNA in association with tumor tissue entities and analyse tumor-specific eRNA; (b) analyse the expression and function of RNases in tumor and endothelial cells; (c) characterize eRNA-dependent cellular activities of tumor cells (proliferation, migration) and endothelial cells (permeability, angiogenesis) as well as identify eRNA-dependent receptor/signaling pathways; (e) describe the mechanism of eRNA-related tumor-associated hypercoagulability in different tumor models, and pursue the concept that RNases may serve as novel anti-tumor modality. Results from these proposed in vivo and in vitro experiments will gain novel insights into eRNA-dependent molecular and cellular interrelations of the tumor-vessel interface with the possibility to apply promising strategies for tumor therapy.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1190: The Tumour-Vessel Interface