Plasminogen binding and activation at the breast cancer cell surface: the integral role of urokinase activity

Abstract

Introduction The regulation of extracellular proteolytic activity via the plasminogen activation system is complex, involving numerous activators, inhibitors, and receptors. Previous studies on monocytic and colon cell lines suggest that plasmin pretreatment can increase plasminogen binding, allowing the active enzyme to generate binding sites for its precursor. Other studies have shown the importance of pre-formed receptors such as annexin II heterotetramer. However, few studies have used techniques that exclusively characterise cell-surface events and these mechanisms have not been investigated at the breast cancer cell surface.

Soluble M6P/IGF2R Released by TACE Controls Angiogenesis via Blocking Plasminogen Activation

“…Peptide 18-36 blocked the cell surface binding by 45% compared to scrambled peptide ( Figure 3A). Because it had been shown before that a direct interaction between uPA and Plg was necessary for Plg activation on the cell surface, 30,31 we tested whether sM6P/IGF2R and peptide 18-36 were able to block this interaction. An in vitro binding assay revealed that similarly to TA, sM6P/IGF2R and peptide 18-36 both blocked the interaction between Plg and uPA ( Figure 3B).…”

Tripeptides with non-code amino acids as potential serine proteases inhibitors

“…It was found that the proteolytic activity of uPA is closely related to cell-surface events when incubated with the breast cancer cells. MCF-7 had low uPAR/uPA-expressing and low plasminogen-binding, whereas MDA-MB-231 had high uPAR/uPA expressing and high plasminogen binding 29 . Due to synthesized peptides would be rather nontoxic to MCF-7 cancer cells.…”

Plasminogen and angiostatin levels in female benign breast lesions

“…The interpretation of this result may be that cells of benign tissue lumps can expose a number of molecules, which participate in Plg/AS binding with cellular surface. A variety of proteins, including actin, annexin II, S100A10, cytokeratin 8, tetranectin and αenolase have been identified as potential Plg receptors on the surface of certain types of human breast cancer cells [30]. AS appeared to effectively interact with some Plg receptors.…”