Research Groups - Biochemistry
Role of proteolytic enzymes in tumor invasion and extracellular matrix degradation
Erkki Koivunen, PhD, Docent
We study the function of proteinases in tumor cell migration, invasion and metastasis. A key step in cell motility is the degradation of extracellular matrix and other tissue barriers that restrict cell movement. An important research tool for these studies is the phage display of peptide libraries which express most permutations possible for short peptides. By screening such libraries we have found novel proteinase inhibitors and, in addition, identified interacting proteins that are essential for proteinase function.
Peptide library display on filamentous phage
Direct binding of matrix
metalloproteinases to integrins is believed to be n eeded for accurate timing of pro-matrix metalloproteinase activation and for focusing the proteolysis pericellularly
to integrin contact sites. We study how integrins and matrix metalloproteinases co-operate and mediate the movement of
cells. Many diseases of man such as cancer and certain inflammatory conditions are characterized by uncontrolled mass
movement of cells, which is accompanied by tissue degradation. Our goal is to develop potential anti-cancer agents
either by blocking the enzyme activity of proteinases or by interfering with their association with integrins.
Invadosome- a cell surface complex of the gelatinase with integrin and other molecules.