Development of diagnostic and prognostic extracellular matrix signatures for human colon and pancreatic carcinomas

• Applicant: Dr. Steffen Rickelt
• Subject Area: Pathology ; Cell Biology
• Term: from 2013 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 232515388

The extracellular matrix (ECM) is a fundamental and important component of the metazoan body. The ECM is involved in cell signaling, intercellular communication as well as cell and tissue protection, and it provides biophysical and biochemical functions that are important regulators of cell proliferation, cell apoptosis, cell differentiation and migration. Over the past years it has become increasingly clear that changes of the ECM are also associated with various diseases such as fibroses, wound healing and scar formations, skeletal disorders and cancer. However, the biochemical composition of the ECM in different tissues and during disease changes is still only poorly understood. Therefore, a broader basis for understanding the ECM composition, structure and assembly would significantly help to comprehend the complex dynamics of development and diseases, including tumor formation and invasion as well as metastasis.The Hynes laboratory has recently established strategies and methods to characterize and analyze the in vivo ECM of normal and diseased tissues by the enrichment of the insoluble ECM complement in combination with detailed proteomic and bioinformatic analyses. Using these techniques it is now possible to catalogue the ensembles of ECM and ECM-associated molecules, i.e. the “matrisome”, of a particular normal or diseased tissue, including tumors, and to characterize the differences between the matrisomes of various tissues and their changes during pathogenesis. In general, it is expected that this approach will allow the identification of diagnostic and prognostic ECM “signatures” that are valuable in diagnoses, prognoses and the clinical management of specific diseases.The major aim of the proposed study will be the selection of ECM antigens, followed by the generation of antibodies specific for such signature molecules in human colon and pancreatic carcinomas, and the development of protocols for the establishment of robust immunohistochemistry (IHC) methods that can be applied in routine pathological analyses as well as in special IHC and immunoelectron microscopic studies. Moreover, the functional roles of the appropriate molecules that show interesting changes in the course of a disease will be analyzed by different loss- and gain-of-function manipulation techniques, including murine tumor models.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Richard O. Hynes