BBB Seminar: Thomas Seufferlein
Regulation of tumor angiogenesis by protein kinase D2
Department of Internal Medicine I, University Clinic and Polyclinic for Internal Medicine, Martin-Luther University Halle-Wittenberg, Halle (Saale), Germany
Protein kinase D (PKD) isoenzymes have been implicated in VEGF-A induced regulation of endothelial cell proliferation and migration. We demonstrate that PKDs are major regulators of tumor angiogenesis. We examined the role of PKDs in tumor angiogenesis both in epithelial tumor cells and in the endothelium using distinct in vitro and in vivo model systems and selective targeting of PKD2 in the endothelium and the tumor, respectively. Depletion of PKD2 in pancreatic cancer cells interrupted the crosstalk between tumor and vessels and substantially inhibited tumor-driven blood vessel formation and tumor growth both in the CAM model and in an orthotopic model of pancreatic cancer in athymic mice. These data show a novel, essential role of PKD2 in two key aspects of tumor angiogenesis, VEGF expression and secretion by the tumor cells and VEGF-stimulated blood vessel formation by the tumor-associated endothelial cells.
Chair: Alexandre Micoulet, Department of Biomedicine