Cancers are today viewed as tissues comprised by tumor and non-malignant host cells which cooperatively contribute to tumor progression, immune suppression and therapy resistance. Reprogramming of non-malignant cells, such as immune cells, is not only directed by genetic alterations in tumor cells but also mediated by the intercellular communication between host and tumor cells within the tumor microenvironment (TME). The tumor secretome mediating this communication comprises factors released by both cancer and host cells, including soluble factors and extracellular vesicles (EVs). The tumor secretome therefore holds great promise as a source of biomarkers and a target for innovative therapeutic approaches. However, the composition of the tumor secretome and the functional impact of individual components on the interaction of tumor cells and host cells remain to be investigated in detail. The Research Training Group (RTG) focuses on several tumor entities that are critically dependent on the TME such as ovarian cancer, pancreatic cancer and acute myeloid leukemia. Of particular interest is the role of NF-κB and p53-regulated secretome components, including EVs, that modulate the plasticity of tumor-associated immune cells, non-malignant bystander cells (see figure), cancer cell invasion, metastasis, and resistance to therapy. In addition, the importance of the chemotherapy-induced secretome and the ensuing DNA damage in the anti-tumor immune defense is investigated.
The distinguishing feature of the RTG is the focus on primary patient-derived samples and in vitro models to study cellular interactions within the TME mediated by the secretome. The experimental models of patient-derived tumor and host cells used in the individual projects allow genetic and pharmacologic loss- or gain-of-function approaches in co-culture and 3D models. We expect that this work will generate new clinically relevant insights into the pathological and diagnostic role of the tumor secretome, which cannot be achieved in animal models or with ordinary tumor cell lines. Our approach is feasible since biomaterial (tumor cells, peripheral blood cells, plasma, ascites) and corresponding clinical data have been collected over the past years, establishing/setting a unique sample pool that can be used to comprehensively analyze the tumor secretome in the above-mentioned model diseases.
The RTG 2573 comprises a total of eleven individual projects. Nine of the projects are led by scientists from Marburg, two projects by researchers from Giessen. Participants from Marburg are Andreas Burchert, María Gómez-Serrano, Magdalena Huber, Robert Liefke, Rolf Müller (vice spokesman of the RTG), Andreas Neubauer, Elke Pogge von Strandmann (spokeswoman of the RTG), Silke Reinartz, Thorsten Stiewe, Uwe Wagner and Thomas Worzfeld. From the Justus Liebig University Giessen are involved: Michael Kracht and Lienhard Schmitz. We aim to establish an internationally competitive research center for the structured training of outstanding PhD/MD students in this emerging field to contribute to the development of an internationally attractive scientific environment for tumor research. Students of natural sciences and medicine are the target groups of the program.