Abstract
It is well established that proteolytic enzymes play a significant role in the expression of the malignant phenotype including the loss of growth regulation, invasiveness, and formation of metastases (Liotta et al., 1991). Tumor cellderived proteases have multiple activities and have been shown to degrade basement membrane components, stimulate angiogenesis, and promote tumor cell proliferation and migration. Tumor cells may also be responsible for the elaboration of proteolytic enzymes by host cells such as the endothelium, stroma, or components of the immune system. Studies using an in vitro amnion invasion assay, shown to provide a rigorous test for tumor cell invasion in vivo (Yagel et al., 1989), suggest the involvement of a protease cascade in the invasion process. Although there is some controversy regarding the specific proteases participating in the cascade, plasminogen activator, plasmin, stromelysin, type IV collagenase, and interstitial collagenase appear to be important (Ostrowski et al., 1986; Persky et al., 1986; Whitham et al., 1986; Mignatti et al., 1987; Strous et al., 1988). Tissue-type plasminogen activator has been identified in breast cancer cytosol and its concentration may be of some prognostic significance (Duffy et al., 1988). There is also a large body of evidence suggesting that metastasis is facilitated by thrombus formation (Saito et al., 1980; Gasic et al., 1983). Tumor cells have been shown to induce platelet aggregation through the generation of thrombin and a specific membrane protein responsible for thrombin generation has been isolated from several tumor cell lines (Cavanaugh et al., 1988).
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Finlay, T.H., Kadner, S.S., Tamir, S. (1993). Protease Inhibitor Synthesis by MCF-7 Breast Cancer Cells. In: Troll, W., Kennedy, A.R. (eds) Protease Inhibitors as Cancer Chemopreventive Agents. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2882-1_8
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