Unraveling the role of proteases in cancer

Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, 540 E. Canfield, Detroit, MI 48201, USA.
Clinica Chimica Acta (Impact Factor: 2.82). 03/2000; 291(2):113-35. DOI: 10.1016/S0009-8981(99)00224-7
Source: PubMed


Investigators have been studying the expression and activity of proteases in the final steps of tumor progression, invasion and metastasis, for the past 30 years. Recent studies, however, indicate that proteases are involved earlier in progression, e.g., in tumor growth both at the primary and metastatic sites. Extracellular proteases may co-operatively influence matrix degradation and tumor cell invasion through proteolytic cascades, with individual proteases having distinct roles in tumor growth, invasion, migration and angiogenesis. In this review, we use cathepsin B as an example to examine the involvement of proteases in tumor progression and metastasis. We discuss the effect of interactions among tumor cells, stromal cells, and the extracellular matrix on the regulation of protease expression. Further elucidation of the role of proteases in cancer will allow us to design more effective inhibitors and novel protease-based drugs for clinical use.

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    • "The low activity of these enzymes in blood is because of presence of endogenous inhibitors and unfavorably high pH value of blood as compared to lysosomes [40]. Peptide-based linkers are completely hydrolyzed into the tumor mass due to the presence of proteases and release the potent drug [41]. Peptide linkers have been extensively used for the development of ADCs using different potent drugs [22,42–44]. "
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    • "In this context, nanocarriers should release their drug payload only in response to specific physiological changes naturally occurring within tumors, such as the presence of high concentrations of matrix metalloproteases (MMPs) (Basel et al., 2011; Nagase and Woessner, Jr., 1999; Kugler, 1999; Sawant et al., 2006). MMPs are proteolytic enzymes overexpressed in tumors, which are involved in a number of biological mechanisms and catalytic activities related with tumor progression (Koblinski et al., 2000; Zucker, 1988). In particular, MMP2 (also known as gelatinase A; Mw: 72 kDa) hydrolyzes type IV collagen, which is a major constituent of tumor extracellular matrix (ECM), thus resulting in enhanced tumor progression (Klein et al., 2004), invasion and angiogenesis (Holle et al., 2003). "
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