Objective
Different types of tissue-associated proteases are involved in extracellularmatrix turnover in pathological conditions: 1) Matrix metalloproteases MMPs2) Cysteine proteases cathepsins B,L 3) Aspartyl protease cathepsin D4) Serine proteases plasmin and urokinase-type plasminogen activator (uPA).For invasion to take place, attachment of tumor cells to and subsequent releasefrom extracellular matrix components involving proteolysis must occur in acontrolled fashion; successful tumor cell invasion requires a balance ofproteases and protease inhibitors (limited proteolysis). Basic and clinic oriented research on tissue-associated proteases is strong in the EU member staNumerous studies on the biological and/or clinical significance of proteasestheir inhibitors and receptors under physiological and pathophysiologicalconditions have been initiated in Europe by members of this Concerted European Action: CLINICAL RELEVANCE OF PROTEASES IN TUMOR INVASION AND METASTASIS(Contract BMHl-CT93-1346; coordinator: M.Schmitt Frauenklinik TU Munchen, GermProteases and their inhibitors are of high clinical relevance for selection of high-risk groups and in predicting response to adjuvant hormone or chemotherapyThey may serve as predictive and/or prognostic factors in cancer of the breast,ovary, lung, kidney, cervix uteri and of the gastrointestinal tract. Most of thfindings, especially on uPA and cathepsin D have been made by members of thisConcerted European Action: The biological and clinical relevance of cathepsins B,L, metalloproteases and respective inhibitors in cancer progression has only recently been published. The present Concerted European Action is concerned witclinical impact of proteases and their inhibitors and receptors for prognosis(relapse-free and overall survival) and clinical decision making (adjuvant therThe very promising recent results on uPA, PAI-1, cathepsins and/or metalloproteto act as prognostic factors in cancer of the breast, ovary, stomach, colon andhave definitely stimulated eastern European partners to become a member of thisconcerted action 1) V. Turk, Ljubljana, Slovenia 2) G.Georgiev Moscow, Russia Zlatoidsky, Mostar, Slovakia 4) T.Davidenko Odessa, Ukraine 5) A.Kaban Kiev, They will be addressing the proteolytic mechanisms which underscore the invasivof tumor cells. These new activities aim at the development of novel biologicaltreatments which attenuate the invasiveness of tumor cells and may consequentlysurvival and the quality of life of patients afflicted with the disease by appltypes of agents directed to tumor-associated proteases.
Call for proposal
Data not availableFunding Scheme
CSC - Cost-sharing contractsCoordinator
81675 München
Germany