Vascular Biology in Cancer

Principal Investigator
Ass.-Prof. Doz. Dr. Gerald Prager
deutsche Version deutsche Version

General Information
The research interest of this cell biology group is focused on vascular biology in cancer, thereby focusing on proangiogenic endothelial cell behavior. Through Dr. Prager’s clinical training for hemato-oncology, he became a member of the sought after group of medical researches, who achieved his expertise in international renowned labs at University of California, San Diego and the Department of Vascular Biology. His work is honored by 15 international awards and resulted in publications in international highly renowned peer-review journals. This young research group is embedded in an international cancer research campus associated with MUV and is in tight collaboration with Dr. M. Ginsberg, UCSD and the Department of Vascular Biology, MUW and other international and national research groups.

Thereby, one aim is defined to characterize the complex mechanisms of the urokinase receptor (uPAR) interactom, which regulates pro-angiogenic endothelial cell migration by redistributing integrin adhesion receptors. Thereby, the multimolecular complex formation, which includes direct interaction with integrin adhesion receptors, is investigated, as the uPAR interactom represents a prerequisite for integrin internalization and redistribution during endothelial cell migration. uPAR dependent integrin internalization and redistribution is a prerequisite for endothelial cell detachment at the trailing end. uPAR and integrin adhesion receptors are redistributed to the leading edge, and are found to be co-localized in newly formed focal contacts. Interference with this chain of events at different steps affects integrin-induced outside in signaling, endothelial cell migration and survival, which impairs angiogenesis, a prerequisite of tumor growth and metastasis. Another aim of the research group is defined by characterization of the role of integrin-induced signal transduction in tumor cell behavior. For effective tumor growth the intracellular sub-domain of integrin beta subunits are known to be essential. CD98hc, a type II transmembrane protein, thereby mediates ‘outside-in’ signaling via direct interaction with a conserved motif within the cytoplasmic domains of integrin beta-1A and beta-3. By interfering with this mechanism, the role of CD98hc / integrin interaction is studied, which might lead to novel therapeutic strategies in cancer. Furthermore, the research group is investigating a novel and hitherto undescribed function of the carcinoembryonic antigen (CEA) in tumor angiogenesis. CEA, by binding to its putative receptor CEAR, induces angiogenic endothelial cell behavior such as endothelial cell migration and proliferation in vitro and in vivo. Thereby, intracellular signal transduction is induced, leading to activation of the MEK / ERK- as well as the PI3k / Akt- pathways, both in an integrin beta subunit dependent manner. Currently, the interest of research is focused on potential CEA / CEAR complex interaction with integrin adhesion receptors.

Lab Personnel

Department of Medicine I
Division of Clinical Oncology
Waehringer Guertel 18-20
AT-1090 Vienna, Austria
FAX: +43-1-40400-44510

Ass.-Prof. Doz. Dr. Gerald Prager
Pricipal Investigator

Mag. Marina Poettler
Ph.D. student

Dr. Matthias Unseld
Research Associate and Ph.D. student

Dr. Nishamd Geetha
Postdoctoral Fellow

Dr. Kira Braemswig (in Karenz)
Research Associate