Final Report Summary - CAFFEIN (Cancer Associated Fibroblasts (CAF) Function in Tumor Expansion and Invasion) Final publishable summary reportCancer is a major cause of death worldwide. A novel way to treat cancer is not only to target the genetically unstable cancer cells directly, but in addition also the surrounding stroma cells, which are genetically stable. One of these tumor stroma cells are the cancer associated fibroblasts (CAFs), which produce matrix proteins such as collagens, matrix degrading enzymes, and various growth factors, which promote tumor growth, progression, invasion, and therapy resistance. The CAFFEIN network (www.caffein.ku.dk) was investigating “CAF function in Tumor Expansion and Invasion” by a collaborative research interaction of industrial and academic scientists. Major questions being addressed were the identification of markers for CAF subpopulations, improved molecular understanding of the mechanisms how CAFs promote tumor development, and the identification of targets to eliminate CAFs or impair their cancer promoting effect.The CAFFEIN network consisted of 10 leading European CAF research groups in 7 different countries as academic beneficiaries and one biotech company in another European country as industrial beneficiary. It trained 9 PhD students from 7 European countries, 1 PhD student from China, and 3 postdocs from 3 European countries. Thus, CAFFEIN integrated complementary skills and knowledge of an international and diverse mix of scientists and students, which proved to be highly synergistic and was crucial for the success of the project.As a training network, CAFFEIN aimed at providing young scientists with state-of-the-art knowledge in CAF biology and methods to investigate CAF function in cancer. Furthermore, the PhD students and post docs were trained in complementary skills to increase their chances of employment in industry and academia.The CAFFEIN project was divided into six workpackages of which the first three focused on the research training (Functional CAF subpopulations; CAF effector mechanisms; Therapeutic antibodies). Workpackage 4 described the network wide training events, while the remaining project parts outlined the planned outreach activities and the management structure.The CAFFEIN fellows, 10 PhD students and 3 post docs, received research training in their home laboratories and, through secondments, and in partner institutions. Local PhD schools provided training in different biological areas, safety and ethics. Network wide training specific for the CAFFEIN fellows endowed the fellows with expert knowledge in CAF biology and function, specialized techniques in cancer research, complementary skills important in pharmaceutical industry, and complementary skills important for the initiation of biomedical start-up companies and clinical studies. Within the CAFFEIN project three international symposia and one 2-day conference were held, where the CAFFEIN fellows participated with oral presentations and posters, thus increasing their presentation skills as well as their international network. In addition, CAFFEIN fellows participated on 32 occasions at other international scientific conferences to discuss their scientific findings with experts in the field.During the project period the CAFFEIN fellows developed a strong group feeling, despite being scattered all over Europe. They started a Facebook group, exchanged scientific tools, gave each other advice on the projects, and became inspired to novel experiments by learning from each other. These frequent interactions by far exceeded our initial expectations and are one of the reasons for the success of CAFFEIN both with respect to the training as well as to the scientific results.The CAFFEIN project achieved a number of exciting results:• Description of a CAF-equivalent cell population in glioblastoma• Identification of a novel CAF-specific function of a tumor suppressor gene• Description of the function of exosomes and exosome-encapsulated miRNA in CAF differentiation • Analysis of the role of CAF exosomes in cancer progression• Analysis of function of #11 integrin on CAFs in CAF development and in skin and breast cancer• Analysis of the role of laminin binding integrins in CAF differentiation and function• Analysis of the role of collagen XV in CAF differentiation and function• Identification of a novel role for the small GTPase RhoA in CAFs in CAF-dependent cancer cell invasion• Analysis of the ECM secretome of prostate cancer CAFs• Development of a high-throughput assay to study CAF-cancer cell interaction• Identification of CAF specific antibody mimeticsThese findings resulted up to now in 5 publications and 13 manuscripts, but more are expected, since 8 fellows decided to continue their PhD over the 3-year CAFFEIN-funded period. The fact that they all could obtain financial support for this additional research based on their results achieved, strongly indicates the importance of their findings. Two CAFFEIN fellows have already submitted their thesis and one of them defended it already successfully.Our results contribute to a deeper understanding on how cancer related fibrosis is developing and how it contributes to disease progression. This work identified novel drug targets that could prevent cancer related fibrosis and inhibit cancer promoting effects of CAFs. Furthermore, we identified with our industrial partner potential drugs targeting CAFs (antibody mimetics) and developed screening procedures to search for drugs preventing CAF formation. These results will be followed up and are expected to contribute to new therapies for cancer patients improving their life expectancy and their quality of life. In addition, our research will contribute to new jobs in the pharmaceutical industry in Europe.Different outreach activities took place to inform a broader public about CAFFEIN. Using oral presentations, articles, activities and web based tools we tried to reach scientists, students, school children and interested laymen and informed them about CAFs, the CAFFEIN network, our goals and our results.Five of the 10 CAFFEIN PhD fellows and all three CAFFEIN post doc fellows are female, indicating the successful implementation of gender equality, which was achieved without compromising on scientific excellence.Taken together, we strongly feel that both with respect to training as well as to scientific results the CAFFEIN project exceeded the high expectations. As a consequence of this successful interaction, the CAFFEIN partner institutions are trying now to further formalize their collaboration by establishing joint PhD programs. Although it is clearly a challenge to “fuse” national PhD programs on a European level, the good experiences from the CAFFEIN interaction convinced us that the benefit of increased European interaction is more than worth the additional administrative work.