Cell-Associated Plasminogen Activation: Regulation And Physiological Functions

p53 dominant-negative mutant R273H promotes invasion and migration of human endometrial cancer HHUA cells

“…All three of these genes were shown to negatively modulate tumor invasion and migration. PAI-1 can reduce invasiveness in breast and ovarian cancer cells [27,28]. Maspin, a tumor-suppressing serpin (serine protease inhibitor) has been shown to suppress tumor cell invasion [29] and cell motility [30].…”

76 Reduced transplant arteriosclerosis in plasminogen deficient mice

“…The Plg system may contribute to cell invasion in several manners: (a) via plasmin-mediated degradation of extracellular matrix components (9, 11); (b) via plasmin-mediated activation or liberation of chemotactic growth factors sequestered within the matrix, such as hepatocyte growth factor, basic fibroblast growth factor, vascular endothelial growth factor, or TGF-␤1, which would attract leukocytes into the media or stimulate smooth muscle cells to emigrate into the intima (25)(26)(27); (c) via intracellular signaling mediated through the u-PAu-PAR pathway (28); or (d) via an effect on cell-matrix interactions through a molecular interplay between u-PA, u-PAR, PAI-1, vitronectin, and integrins (29). Although direct evidence for the latter three hypotheses is not available, their possible involvement cannot be excluded either.…”

39 Structure function relationships of plasminogen activator inhibitor type-2 (PAI-2)

“…As detailed in following sections, uncontrolled proteolysis and subsequent tissue damage is prevented by precise and coordinated regulation of the PA system on a number of levels. These include cytokine and hormonal control of gene expression, localisation of various components of the system via binding to various ECM proteins and cell-surface receptors, clearance of free and inhibited plasminogen activators via specific cellular receptors, and specific inhibi of both plasmin and plasminogen activators by 0C2-antiplasmin and plasminogen activator inhibitors (PAI-1, PAI-2, PAI-3) respectively (Saksela & Rifkin 1988;Vassali et al 1991;Vassali etal 1992;Pollanen et al 1991) (Figure 1.6).…”

“…In contrast, uPA is expressed in association with its receptor (uPAR) by a number of cell types (eg. peripheral blood monocytes, B lymphocytes, U937 cells, fibroblasts, endothelial cells and a number of malignant cell lines) and is often focused at cell-cell contacts and ECM contacts, implicating it as a key component in ECM degradation and cell migration (Saksela & Rifkin 1988;Pollanen et al 1988;Vassalli et al 1992;). …”

“…Although the catalytic activity of tc-uPA is 200-1000 fold higher than scuPA, limited evidence exists for the activation of plasminogen by sc-uPA under physiological conditions (eg. when immobilised via lysine dependant binding to cellular receptors), a potentially important regulatory mechanism for uPA mediated plasminogen activation (Saksela & Rifkin 1988). The proteolytic activity of uPA is facilitated by the catalytic triad of Asp 275 , His 224 and Ser 376 (Verde et al 1984).…”