The Role of Lysosomes in the Cancer Progression: Focus on the Extracellular Matrix Degradation

Abstract

Lysosomes are multifunctional cell organelles that not only provide degradation of macromolecules by lumenal acid hydrolases, but also contribute in the regulation of cell metabolism, ion homeostasis maintenance, and programmed cell death induction. The study of this compartment in various pathological conditions, including the oncological diseases by different origins is of particular interest. This article discusses the lysosome involvement in the process of malignant cell transformation, as well as the role of these organelles in the tumor cell metastasis mediated by proteolytic cleavage of the extracellular matrix components. Metabolic and morphological changes of cells during oncogenesis lead to pHdependent redistribution of lysosomes within the cell, accompanied by the secretion of lysosomal proteases cathepsins into the extracellular space. Cysteine, serine, and arginine cathepsins released by both tumor cells and tumor-associated cells catalyze the cleavage of various components of the extracellular matrix and basement membrane, or proteolytically activate other enzymes also involved in this process. In this instance, lysosomal proteases directly affect the ability of cells to invade and the metastatic potential of tumor formation. In addition, it was demonstrated the prognostic importance of some cathepsins (especially cathepsins B, K, and D) the number and activity of which in the tumor tissue and its microenvironment are associated with malignancy of the formation, as well as with a poor prognosis for patient survival and with the possibility of recurrences.