Squamous Cell Carcinoma Cells Invasion in RDEB patients: Role of Stromal Fibroblasts and Collagen VII Depletion in the Invasive Process (Gaggioli 1)

Short lay summary

Despite tremendous efforts by scientists and clinicians over the last two decades, patients suffering from recessive epidermolysis bullosa (RDEB) are still prone to develop aggressive and metastatic skin cancers with fatal demise. Our original study recently showed a new role for the tumor-associated fibroblasts in the invasion and metastatic development of skin cancers due to their ability to make tracks and to remodel the tissue surrounding the tumor. Blockade of such remodeling capacities of the fibroblasts, using appropriate drugs is expected to hamper cancer cell invasion.
We have shown that similar to cancer-associated fibroblasts (CAF), skin fibroblasts in RDEB patients with no apparent cancer lesions are able to induce a migratory and behavior in skin cancer cells. The aim of this present project is to confirm the role of RDEB-fibroblasts in RDEB patients skin cancer development and dissemination. Using a chemical screening approach, that we have successfully validated using non DEB-tumor CAF, we shall identify appropriated drugs active in blocking the ability of RDEB-fibroblasts to produce a potent microenvironment for skin cancer invasion. The large scale screening approach, based on the microenvironment remodeling capacity of the fibroblasts, coupled to signal transduction studies will also allow us to decipher the signaling pathways underlying the aggressive behavior of SCC in RDEB and identify new potential molecular targets for drug therapies.