One hallmark of cancer is the misrouted interplay of mutated cells with surrounding cells and the extracellular matrix (ECM). On the molecular level these interactions base on transmembrane cellular ligands like cadherins and integrins. In malignant melanoma, cadherin and integrin expression are often dysregulated. Our aim is to gain further insight into the relevance of certain ligands relevant for tumor cell functions. We are especially interested in the relevance of so far underestimated biophysical aspects regulating ligand interactions. Using biomimetic model-systems we analyze how biophysical parameters like ligand density, tissue stiffness and ligand topography might influence tumor progression.
Signaling pathways regulated by the extracellular matrix
Recognition of ECM binding sites results in integrin clustering and activation of the cytoskeleton. In addition, certain features of the ECM like a high amount of collagen also influence survival pathways in malignant melanoma. Melanoma cells themselves contribute to modification of the ECM by deposition of collagen and cleavage of ECM components. Thus, reciprocal interactions between the ECM and tumor cells might be relevant in tumor progression or drug resistance. We aim to identify relevant cellular receptors and signaling pathways enabling tumor cells to abuse certain ECM features for their own growth and spread to address the “fatal” interplay of tumor cells with the ECM.