GRK 2573:  The inflammatory tumor secretome – from understanding to novel therapies

• Subject Area: Medicine
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 416910386

It is generally accepted that tumor initiation and progression depend on the reciprocal cross-talk between tumor cells and non-malignant cells including immune cells, fibroblasts, and adipocytes. These cells are recruited into the tumor tissue and are remodeled to establish a tumor microenvironment (TME), which then supports all hallmarks of cancer. The interaction of tumor cells and non-tumor cells within the TME is mediated by direct cell-cell interaction and by secreted factors such as soluble molecules and extracellular vesicles (EVs) collectively referred to as the tumor secretome. Recently, the tumor secretome has emerged as a key player in tumorigenesis and for the response to therapy and holds great promise as a source for novel cancer biomarkers and drug targets. However, its composition and impact on the reciprocal cross-talk of tumor cells and host cells remain to be investigated in detail. Building on discoveries from the first funding period we will decipher molecular mechanisms driven by NF-κB-dependent and p53-regulated secretome components including soluble proteins, metabolites, and EVs, which modulate the plasticity of tumor-associated TME cells. All projects focus on the secretome composition and its impact on the reciprocal cross-talk of tumor cells and host cells in different tumor entities. Distinguishing features of the RTG are the focus on primary patient-derived samples and in vitro models including organoids and a strong interest in the role of EVs in the TME. Our education program will provide a theoretical and practical basis for the comprehensive investigation of the tumor secretome aiming at better understanding fundamental molecular mechanisms and recognizing and developing their translational potential. We integrate basic and medical students as early as possible into scientific projects and the training program to support their steps to scientific independence. Coordinated theoretical as well as practical courses and an internship/fellowship program are part of the structured curriculum. State-of-the-art methods covering omics technologies, bioinformatics, imaging methods, in vitro cell culture models, and mouse tumor models are conveyed by the participating research groups and by established core facilities with outstanding expertise in the specific topics, technologies, and methods. This will allow the investigation of the cellular communication within the TME focusing on the secretome on an internationally high professional level. Altogether, these measures will educate a new generation of scientists engaged in tumor biology in general and tumor secretome research, in particular, addressing both, basic scientific questions and translational cancer research. This will open career possibilities in academic research and beyond, such as industry, academic management, or society in general.

• DFG Programme: Research Training Groups
• Applicant Institution: Philipps-Universität Marburg
• Participating Institution: Justus-Liebig-Universität Gießen
• Spokesperson: Professorin Dr. Elke Pogge von Strandmann
• Participating Researchers: Dr. Bilal Alashkar Alhamwe; Professor Dr. Andreas Burchert; Dr. Miriam Frech; Dr. Niklas Gremke; Dr. María Gómez-Serrano; Professorin Dr. Magdalena Huber; Professor Dr. Michael Kracht; Dr. Robert Liefke; Silke Reinartz, Ph.D.; Professor Dr. M. Lienhard Schmitz; Professor Dr. Thorsten Stiewe; Professorin Dr. Regina Verena Taudte; Professor Dr. Thomas Worzfeld