Construction of mini collagen ligands recognized by alpha2beta1 integrin and CD44/CSPG melanoma receptors: New method for the study of signaling pathways

The metastatic process involves tumor cell adhesion to basement membrane components, such as type IV collagen. A specific mitogen activated protein kinase cascade is activated by cell adhesion to type IV collagen. This activation causes the expression of proteolytic enzymes. These enzymes will then participate in compromising extracellular matrix components and enhance cell movement through them. To better understand tumor invasion of type IV collagen, we have constructed triple-helical peptide (THP) ligands for melanoma cell receptors, and used these ligands to determine if receptors such as CD44/CSPG and the alpha2beta1 integrin have unique matrix metalloproteinase (MMP) signaling pathways affected by the tyrosine kinase inhibitor genistein. MMP protein expression profiles were evaluated using the alpha2beta1 integrin ligand, and CD44/CSPG ligand. Results were indicative of specific activation sequences that tumor cells undergo upon binding to select regions of type IV collagen.