COLLAGEN MATRIX REMODELLING AS A FACTOR of TUMOUR PROGRESSION AGGRESSIVENESS: THE ROLE OF PROTEASES AND CROSS-LINKING ENZYMES

Collagen matrix remodelling is one of the key processes determining the progression of malignant tumours and the development of an aggressive tumour phenotype. This review summarises current data on the role of collagen degradation and cross-linking enzymes in the progression of malignant tumours. It is shown that an imbalance between the processes of degradation and stabilisation of collagen fibres contributes to increased tissue stiffness and the activation of signalling pathways associated with invasion and metastasis. The review focuses on matrix metalloproteinases, cathepsins, meprins, lysyl oxidases and enzymes of the procollagen-lysine family, 2-Oxoglutarate 5-Dioxygenases (PLODs) as enzymes involved in extracellular matrix remodelling, regulation of the epithelial-mesenchymal transition, and the progression of malignant tumours. The results of recent studies demonstrating the link between abnormalities in the expression of collagen-modifying enzymes and the aggressiveness of the tumour process in patients with various types of cancer have been analysed.