“Pathogenic Impact of the Interplay of Inflammation and Blood Vessels in Colorectal Carcinoma and Inflammatory Bowel Diseases”, Michael Stürzl, Medical Immunology Campus Erlangen, Germany
Speaker: Michael Stürzl, Medical Immunology Campus Erlangen, Germany
Host: Postdoc Network DKFZ
Colorectal cancer (CRC) and inflammatory bowel diseases (IBD) are very common and pathogenically related diseases in industrialized countries. Inflammation and angiogenesis are prominent hallmarks of both diseases. However, the role of the vascular-inflammatory cell interplay in the course of these diseases has not been investigated in detail.
In the past we characterized anti-angiogenic activities of inflammatory cytokines such as IFN-g and identified intracellular mediators thereof. Validating these results in CRC we found that a Th1-like tumor microenvironment (TME) driven by IFN-g inhibits angiogenesis and is associated with improved prognosis of the patients. Moreover, in this TME tumor endothelial cells are maintained in a quiescent state associated with the release of the angiocrine matricellular protein SPARCL1, which exerts anti-tumorigenic activities actively contributing to a less aggressive course of the disease. Interestingly, in IBD it is not the effect on angiogenesis but the induction of vascular permeability caused by the disruption of vascular endothelial-cadherin that mediates the pathogenic effect of the Th1 microenvironment. Genetic or drug-mediated inhibition of Th1-induced vascular permeability ameliorates the disease development independently of the angiogenic activity. Our results demonstrate that the interplay of blood vessels and the inflammatory microenvironment plays an important pathogenic role in IBD and CRC and may be exploited to define new markers of CRC prognosis and/or targets to treat IBD.
Since 2003: C3-Professor and Head of Division of Molecular and Experimental Surgery, Universitätsklinikum Erlangen, Germany
2001 –2005: Head of the Department “Viral Vasculopathy”, tenure, Helmholtz Center Munich, Germany
1999-2001: Leader of the independent Research Group “Viral Vasculopathy”, sponsored by the BioFuture-Program of the BMBF, Helmholtz Center Munich, Germany
1998-1999: Leader of the Research Group “Kaposi’s Sarcoma”, Technische Universität München, Germany
1998: Habilitation in Experimental Pathology, (Max Planck Institute for Biochemistry, Martinsried and Ludwig Maximilians Universität München)
1992-1998: Leader of the Research Group “Kaposi’s Sarcoma”, Max Planck Institute for Biochemistry, Martinsried, Germany
1992: Doctoral thesis (Max Planck Institute for Biochemistry, Martinsried and Ludwig Maximilians Universität München)