Conclusion
DPPIV and seprase are Pro-Xaa cleaving enzymes that form complexes on invadopodia of activated cells, becoming potent ECM-degrading proteases5. The protease complex exerts its mechanism of action on the surface of tissue and cancerous cells that are activated for matrix invasion. Not discussed in this presentation, these peptidases have potential to process bioactive peptides, chemokines and pro-angiogenic peptides, which in turn regulate chemotaxis of leukocytes, endothelial cell sprouting, and the activation of specific cellular function. Here, seprase complexes are shown to be involved in the adhesion to and proteolysis of components of ECM that activate signal transduction for specific cellular activities, including the migration and invasion of stromal and tumor cells.
The main functions of SIMPs reside in their proteolytic and adhesive capacities, thus influencing cellular activities, migration and invasion. These membrane proteases may form physically and functionally linked complexes with other proteases (5) and with integrins (4) at invadopodia, surface protrusions formed during activation of the cell to migrate and invade into the ECM. The capability of DPPIV and seprase to bind multiple molecules allows not only activation of themselves but also association with other membrane proteases and integrins to participate in cooperative ECM protein degradation at invadopodia during cancer invasion and angiogenesis.
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Chen, WT. (2004). DPPIV and Seprase in Cancer Invasion and Angiogenesis. In: Back, N., Cohen, I.R., Kritchevsky, D., Lajtha, A., Paoletti, R. (eds) Dipeptidyl Aminopeptidases in Health and Disease. Advances in Experimental Medicine and Biology, vol 524. Springer, Boston, MA. https://doi.org/10.1007/0-306-47920-6_24
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DOI: https://doi.org/10.1007/0-306-47920-6_24
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