Entwicklung von molekulardiagnostischen Verfahren zur Früherkennung des Pankreaskarzinoms basierend auf sezernierten/freigesetzten Kandidaten-Proteinen

Coordinator:		PD Dr.  Irmgard Schwarte-Waldhoff                                                        Dr. Martina Schnölzer
Institution:		Ruhr-Universität Bochum, Immunologisch-Molekularbiologisches Labor, Med. Universitätsklinik, Knappschaftskrankenhaus,                                   Deutsches Krebsforschungszentrum Heidelberg
Homepage:		www.ruhr-uni-bochum.de

Pancreatic carcinomas for the most part are diagnosed in a late stage, when the chances for cure are low and the tumors often not resectable. Diagnosis usually is made with diverse imaging technologies (sonography, endosonography, MRI, computer tomography, and ERCP) and via detection of tumor markers like CA19-9 and CEA in the blood. All technologies available at present are afflicted with limitations particularly concerning the detection of early tumor stages; consequently, even persons from high-risk groups for the development of this cancer entity can be offered very costly and poorly satisfactory methods, only, for early detection of the disease. This project aims at improved diagnostics via the detection of tumor markers in serum. Candidate markers are discovered using experimental approaches based on cultured tumor cells.
Tumor marker in most cases are proteins released by tumor cells and reaching the blood circulation. A direct access to such proteins is exclusively provided by cell cultures. Therefore we have focused on this particular subproteome tentatively termed the “secretome” for biomarker discovery and have established protocols for the production, enrichment and investigation of such proteins released into the conditioned media of cultured tumor cells. In a cooperation with the DKFZ Heidelberg protein catalogues of such secretomes were established using highly efficient proteomics technologies and used as a basis for the definition of promising tumor marker candidates. These candidates will be assayed with antibody-based and/or mass spectrometry-based methods in order to confirm them in cellular models, in animal models and ultimately in serum samples of carcinoma patients. It is the goal of this project to establish protein signatures, the detection of which in the blood will reach high enough sensitivity for screening high-risk populations (familial pancreatic carcinoma, chronic pancreatitis). The detection of protein biomarker signatures could precede the highly specialized, invasive and costly clinical methods like endoscopic ultrasonography.