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Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human chondrosarcomas

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The aim of the present study was to characterise the ability of malignant chondrosarcomas to invade normal bone by analysing their production of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). For this purpose 12 chondrosarcomas were investigated for the expression of mRNAs for several MMPs and all 4 TIMPs by Northern hybridisation, and for immunohistochemical localisation of the proteins. A characteristic finding of these analyses was increased expression of MMP-13, MMP-14 and TIMP-2 mRNAs in chondrosarcomas when compared with nonmalignant control samples. Individual chondrosarcomas also exhibited elevated levels of MMP-1, MMP-7 and MMP-9 mRNAs. The results of Northern hybridisations were supported by immunohistochemical stainings of the corresponding tumour areas for MMP-2, MMP-14 and TIMP-2, further suggesting that these may have prognostic value for determining whether individual chondrosarcomas are locally aggressive or have a probability of recurrence. Another finding of the present study was a marked heterogeneity in histologic appearance and gene expression of the chondrosarcomas, emphasising the importance of analysing several areas of these tumours to get representative results. These findings suggest that analysis of MMPs could be a useful diagnostic indicator in patients with cartilaginous tumours and could help in differentiating between a low-grade malignant chondrosarcoma and a benign growing enchondroma.

Keywords: Chondrosarcoma; extracellular matrix; human; mRNA; matrix metalloproteinase; tissue inhibitor of metalloproteinase

Document Type: Original Article

Affiliations: 1: Skeletal Research Program, Department of Medical Biochemistry and Molecular Biology, 2: Department of Surgery, University of Turku, 3: Turku Centre for Biotechnology, University of Turku and Åbo Akademi University and Department of Dermatology, Turku, and 4: Department of Pathology, University of Turku and 5: Department of Pathology, Haartman Institute, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland

Publication date: 2001-04-01

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