Proteases of cell adhesion proteins in cancer.

Neoplastic cells elaborate a vast array of proteases that enable them to proteolytically digest underlying adhesion molecules. In doing this, the tumor cell disrupts the adhesive interactions holding it in place so it is free to degrade and migrate through the basement membrane and interstitial stroma resulting in invasion and ultimately metastasis. Invasive cells elaborate specialized membrane protrusions, invadopodia, that actively degrade the underlying substratum. Evidence indicates that integral membrane proteases and receptors for secreted proteases are present on these surface protrusions. All the major classes of secreted proteases are reported to associate with the plasma membrane. Interactions between proteases occurring at the plasma membrane may result in proenzyme activation. It is possible that various proteases in close proximity to each other on the plasma membrane could interact in a proteolytic cascade resulting in in vivo activation, and the subsequent degradation of adhesion proteins.