Proteases as prognostic markers in human and canine cancers

Abstract

The extracellular matrix (ECM) is composed of several types of proteins, which interact and form dynamic networks. These components can modulate cell behaviour and actively influence the growth and differentiation of tissues. ECM is also important in several pathological processes, such as cancer invasion and metastasis, by creating favourable microenvironments. Proteolysis in neoplastic tissues is mediated by proteinases, whose regulation involves complex interactions between neoplastic cells and non-neoplastic stromal cells. In this review, we discuss aspects of proteinase expression and tumor behaviour in humans and dogs. Different classes of proteases are summarized, with special emphasis being placed on molecules that have been shown to correlate with prognosis, reinforcing the need for a better understanding of the regulation of this microenvironment and its influences in tumor progression and metastasis, which should significantly aid the development of improved prognosis and treatment.

Cysteine Cathepsin Protease Inhibition: An update on its Diagnostic, Prognostic and Therapeutic Potential in Cancer

“…All of these approaches look very encouraging and have offered high levels of accuracy and which highlight the therapeutic-targeting potential of cathepsins and their use as reliable prognostic markers [77,78]. However, to avoid controversy stemming from the cell types from which the quantified cathepsin proteases may originate (stromal, tumor or stem cells, for example [79]), future studies may have to be tailored with greater specificity. This could be addressed by testing different patient subgroups at different stages of disease progression.…”

Intratumoral collagen index predicts mortality and survival in canine cutaneous mast cell tumours

“…Conversely, ECM degradation may release factors that stimulate angiogenesis, cell proliferation and migration, or inhibit apoptosis . For example, matrix metalloproteinases (MMPs) are expressed under the influence of the ECM, and facilitate invasion and metastasis via degradation of epithelial and blood vessel basement membranes . Compounds that inhibit the adhesion of cancer cells to the ECM may prevent metastasis …”

An Update on Molecular Pathways Regulating Vasculogenic Mimicry in Human Osteosarcoma and Their Role in Canine Oncology

“…In veterinary literature, current knowledge on the activity and function of proteases and stroma and their relationship with canine cancer malignancy is still limited ( 143 ), despite the fact that MMPs have been widely explored in several human cancers and are strictly related to the VM process ( 144 , 145 ). Inhibition of extracellular proteolysis, in particular of collagenases MMP1, MMP2, and MMP9, is recognized as a valid approach to canine cancer therapy including OSA ( 146 ).…”