Cysteine proteinases in chondrosarcomas

The aim of the present study was to define the role of cathepsins B, H, K, L and S in the pathogenesis of human chondrosarcomas. For this purpose 40 t umour samples obtained from 12 patients with the diagnosis of conventional chondrosarcoma were systematically investigated for the expression of cathe psin mRNAs by Northern hybridisation, and for immunohistochemical localisat ion of the proteins. Northern analysis demonstrated the highest levels of c athepsins B and L in a recurring grade 1 chondrosarcoma, and in a grade 3 c hondrosarcoma and in fibrous histiocytomas. Increased expression of catheps in K mRNA was seen in seven chondrosarcomas, as well as in control tumours; fibrous histiocytomas, osteosarcomas, enchondromas and a giant cell tumour of bone. Cathepsin L was immunolocalised within the large chondrocytes, wh ile cathepsin K was predominantly localised in large multinucleated osteocl astic cells and in some hypertrophic chondrocytes. These results suggest th at chondrosarcoma can be included in the growing list of tumours, where cat hepsins may well be involved in tumour progression. The simultaneous upregu lation of cathepsins B and L, together with matrix metalloproteinase-13, an d the association of cathepsin K with negative prognostic parameters sugges ts that an aggressive biological behaviour of chondrosarcoma may be related to the synthesis of cysteine proteinases and activation of other proteolyt ic enzymes. If this turns out to be the case, cathepsin inhibitors could pr ovide the much needed adjuvant therapy for chondrosarcomas. (C) 2001 Elsevi er Science B.V./International Society of Matrix Biology. All rights reserve d.