In order for transformed cells to progress into aggressive cancers they need to create a tumor-promoting milieu, during the course of their evolution and growth. This occurs through reciprocal interactions with their surroundings. However, new evidence is emerging suggesting that the neoplastic microenvironment may under some circumstances also limit cancer progression. Clinical trials indicate that therapies targeting the tumor stroma are not unequivocally successful, but may in fact aggravate disease, which means that the benefit of such therapies is indication- and context-specific. Therefore, there is an urgent call to address these processes in more detail.
The scientific question of this project is to understand the molecular events that create a tumor-protective and tumor-promoting microenvironment for squamous cell carcinoma of the skin. We will dissect the importance and contribution of specific biological and biophysical alterations to development of invasive cancers by using mouse models, patient tissue samples, organotypic 3D cultures, Caenorhabditis elegans, and a Drosophila tumor model. Mutation-independent changes of both the mesenchyme and the epithelium established before, during, and after malignant transformation will be addressed. Together the studies will, by unraveling specific pro-tumorigenic epithelial cell – microenvironment interactions, help identify therapeutic targets that will not only allow better treatment of solid tumors, but will also provide prophylactic options for individuals genetically and environmentally predisposed to cancer.