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Proteolysis in colorectal cancer.
  1. E A Garbett,
  2. M W Reed,
  3. N J Brown
  1. Professorial Unit of Surgery, North Tees General Hospital, Stockton on Tees, UK. lizbaker@hotmail.com

    Abstract

    BACKGROUND: The process of metastasis is complex, involving many interrelated stages, including proteolysis. Proteolysis occurs in both normal and pathological processes and involves the breakdown of the extracellular matrix and/or basement membrane by proteolytic enzymes. Normally, proteolysis is tightly controlled by specific endogenous proteinase inhibitors. However, in certain disease processes, including cancer, controlled but abnormal proteolysis seems to occur. Proteinases involved in tumour invasion and metastasis include the matrix metalloproteinases (MMPs) and the serine proteinases. AIMS: To gain a greater understanding of the proteolytic process occurring in colorectal cancer and to determine which, if any, proteinases are upregulated. METHODS: The synthesis of proteinases and their inhibitors was compared in paired tumour and normal tissue samples from patients with colorectal cancer (n = 24). Substrate zymography was used to determine the synthesis of MMPs (MMP-2, MMP-9, and MMP-3) and the plasminogen activators (urokinase and tissue-type plasminogen activators); enzyme linked immunosorbent assays (ELISAs) were used to determine the concentrations of MMP-1 and tissue inhibitor of metalloproteinase 1 (TIMP-1); and the technique of quenched fluorescence substrate hydrolysis was performed to determine the total MMP activity of each sample. RESULTS: In general, both proteinase and inhibitor expression was greater in the tumour tissue when compared with the corresponding normal colorectal tissue. The amount of active MMPs was greater in the tumour tissue. CONCLUSIONS: The increased extracellular proteinase concentrations and activity may encourage tumour invasion and metastasis. This study points to MMP-9 as being of potential major importance in the development of this form of cancer.

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