The proteolytic maturation of the metastasis-associated enzymes cathepsin B, cathepsin D and cathepsin L
Abstract
Tumour cell invasion is a complex, multifaceted process, which is initially limited to local spreading of cancer cells into adjacent tissue but ultimately may result in the formation of metastases at distant sites in the body. Proteolytic enzymes, proteinases, are believed to have an essential role in invasive processes, particularly in those steps which require tumour cells to traverse basement membranes and extracellular matrix capsules to enter the surrounding normal tissue. Various proteases are involved in extracellular proteolysis during tumour invasion, including the lysosomal enzymes cathepsin B, cathepsin D and cathepsin L. For instance, the cysteine proteinases cathepsin B and cathepsin L are highly expressed in melanomas and hepatomas, while the aspartic proteinase cathepsin D is a prognostic marker for breast cancer. Our own studies have revealed that elevated cathepsin B synthesis promotes squamous cell carcinoma metastasis. However, it is still poorly understood as to how the overproduction of these enzymes may enhance proteolysis in situ. All three proteinases are initially synthesized as inactive precursors, and maturation of the proenzymes into active forms is a key regulatory step in their biosynthesis. Prevention of proteolytic processing represents therefore an attractive approach to control the proteolytic load in cancerous tissues. To meet this end, it is essential to elucidate the molecular mechanisms which lead to the proteolytic maturation of cathepsins B, D and L in vivo.
proteinase tumor invasion metastases processing
Publikationen
Biosynthesis of lysosomal proteinases in health and disease.
Autoren: Mach, L Jahr: 2002
Journal articles
CA-074, but not its methyl ester CA-074Me, is a selective inhibitor of cathepsin B within living cells.
Autoren: Montaser, M; Lalmanach, G; Mach, L Jahr: 2002
Journal articles
Project staff
Lukas Mach
Univ.Prof. Dipl.-Ing. Dr.nat.techn. Lukas Mach
lukas.mach@boku.ac.at
Tel: +43 1 47654-94065, 94360
Project Leader
01.12.2001 - 31.12.2002