Recent findings indicate that de novo formation of blood vessels from endothelial progenitor cells (adult vasculogenesis) may be responsible for the efficient neovascularisation of tumours. Evidence suggests that tissue kallikrein (hK1) and the kinin peptides exercise important regulatory control on the growth and proliferation of vascular endothelial cells and progenitor cells. Kallikrein inhibitors and kinin B1 and B2 receptor (BKR) antagonists may be therapeutically useful in human lung cancer by reducing vasculogenesis. This project is aimed at investigating potential activators, hK1 and kinin peptides, on the vascular lifeline in lung cancer subtypes. Two distinct processes, vasculogenesis and angiogenesis, are involved in the formation of blood vessels. The existence of putative stem cells in the adult lung has been suggested only recently. In vitro-generated progenitors have been shown to migrate to tumour sites and contribute to cancer vascularization. Recent reports implicate hK1 and BKR in carcinogenesis and vasculogenic effects in lung cancers. hK1 cleaves kininogen to form kinin peptides. We hypothesize that in lung cancer, hK1 and kinin peptides activate endothelial progenitor cells that are quiescent in the parenchyma of the lung.
|Projektleitung:||Univ.-Prof. Dr. Johanna Plendl, Dr. Sabine Käßmeyer|
|Eintragende Einrichtung:||Institut für Veterinär-Anatomie|
|Projektlaufzeit:||01.01.2009 bis 31.12.2010|
|• Titel:||Lung cancer: Activation of stem cells by kallikreins & kinins to form vascular lifelines|
|• Sprecher:||Dr. Sabine Käßmeyer, Prof. Dr. Philip Thompson|
|• Partner:||Professor P. J. Thompson, Director, CAARR and the Lung Institute of Western Australia, Ground Floor, E Block, Sir Charles Gairdner, Hospital,Hospital Avenue, Nedlands, Perth WA 6009|