University homepage Suomeksi På svenska In English
University of Helsinki Faculty of XXX
 

Department of Biological and Environmental Sciences

New websites:

>> Department of Biosciences

>> Department of Environmental Sciences

 

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

 

 

 

 

 



The matrix metalloproteinase inhibitors developed so far include the cyclic peptides
CTT, CRV and PPC, which in mouse models prevent cancer. These peptides have been valuable in identifying the interaction of matrix metalloproteinases with cell surface integrins. Integrins function as cell adhesion receptors and create bonds from the cells to extracellular matrix.

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.

Personnel

Four pre-doctoral students, other MSc. students, a laboratory technician, close collaboration with company called CTT Ltd. that we established in Viikki Biocenter: http://www.cancertargeting.com

Invadosome- a cell surface complex of the gelatinase with integrin and other molecules.