Despite significant advances in cancer research and oncology, metastasis remains the leading cause of cancer-related death. Targeting specific steps of the metastatic cascade such as the acquisition of invasive properties in the primary tumor, the dissemination of cancer cells via the circulation and lymphatics and the establishment of a growth-permissive microenvironment at metastatic sites represents one of the most complex challenges in biomedical research. Many steps of the metastatic cascade are built on the aberrant reactivation of biological processes that are usually only operative in embryogenesis, organogenesis and tissue regeneration. Therefore, a better understanding of these processes in both morphogenesis and disease appears as a promising strategy to identify novel therapeutic strategies for the treatment of cancer. In 2010, this strategy became the mission and overarching theme of then newly established Collaborative Research Center 850 (CRC 850) – Control of Cell Motility in Morphogenesis, Cancer Invasion and Metastasis.
Principle investigators from developmental biology and cancer research joined forces in the CRC 850 to study changes in cell-cell adhesion and cell-matrix interactions as a prerequisite for cell motility during the embryogenesis of model organisms and in the progression of cancer. Investigations on different modes of cellular motility, e.g. the amoeboid or mesenchymal movements of single cells or the collective migration of cell clusters have been in the focus of CRC 850 research, in the context of ontogeny and regeneration but also during metastasis. It is becoming increasingly evident that the initiation of cellular delamination as well as the mode of cellular migration in both development and metastasis are preset by cell intrinsic properties, which are strongly influenced by microenvironmental cues. In cancer cells, altered (epi)genetic programs, e.g. triggered by oncogenic mutations in growth promoting or developmental pathways, can induce reduction of cellular adhesion and increase cellular motility. These changes of cancer cell behavior are less stringently regulated by cell intrinsic oncogenic signaling as hitherto anticipated, since it has been shown more recently that microenvironmental stimuli can modulate these oncogenic signals to revert the high mobility and invasiveness of cancer cells, once they have successfully colonized foreign tissue. The epithelial-to-mesenchymal transition (EMT) and its reversal, the mesenchymal-to-epithelial transition (MET), are well-established mechanisms controlling cellular plasticity. The dynamic switch of cancer cells between epithelial and mesenchymal states – first described for embryonal cells – provides an opportunity for therapeutic intervention, as the transition from one state to the other alters the expression of putative drug targets and affects the proliferative and self-renewing capacity of cancer cells. To implement novel treatment strategies for metastatic disease, the field requires a deeper understanding of the plasticity of cancer cells during the initiation, dissemination and colonization steps of metastasis.
Since 2010, the CRC 850 further promoted cancer research as a major research focus in Freiburg, as reflected by the positive re-evaluation of the Comprehensive Cancer Center Freiburg (CCCF) and the German Cancer Consortium (Deutsches Konsortium Translationale Krebsforschung, DKTK), in both of which several CRC 850 principle investigators are active. The integrated research training group (IRTG) continues to educate a new generation of developmental biologists and cancer researchers. In addition, the CRC 850 runs a seminar series with highly renowned international guest speakers and organizes a bi-annual International Symposium “Control of Cell Motility in Development and Cancer”.
