Regulation of Integrin Function by the Urokinase Receptor

Wei, Ying; Lukashev, Matvey; Simon, Daniel I.; Bodary, Sarah C.; Rosenberg, Steven; Doyle, Michael; Chapman, Harold A.

doi:10.1126/science.273.5281.1551

Cited by 701 publications

(722 citation statements)

References 29 publications

Supporting

Mentioning

683

Contrasting

Unclassified

Order By: Relevance

“…Interestingly, this reduced adhesive capacity of uPAR-del4/5 overexpressing cells was not restricted to the MDA-MB-231 cell line, since transfection of other human breast (i.e., MDA-MB-435, CAMA-1, MCF-7) or ovarian (i.e., OV-MZ-6) cancer cell lines, reduced cell adhesion to various ECM components in the same fashion (Table 1). It is of note that uPAR-WT is an acknowledged pro-adhesive factor, for instance by engagement with its ligand vitronectin, in a number of cell types, including human breast and ovarian cancer cells [26,27].…”

Section: In Vitro Phenotype Of Upar-del4/5 Overexpressing Breast Cancmentioning

confidence: 99%

Overexpression of the urokinase receptor mRNA splice variant uPAR-del4/5 affects tumor-associated processes of breast cancer cells in vitro and in vivo

Sato

Kopitz²,

Grismayer

et al. 2010

Breast Cancer Res Treat

View full text Add to dashboard Cite

show abstract

Section: In Vitro Phenotype Of Upar-del4/5 Overexpressing Breast Cancmentioning

confidence: 99%

Overexpression of the urokinase receptor mRNA splice variant uPAR-del4/5 affects tumor-associated processes of breast cancer cells in vitro and in vivo

Sato

Kopitz²,

Grismayer

et al. 2010

Breast Cancer Res Treat

View full text Add to dashboard Cite

show abstract

“…However, the peptide M25 identified by phage display [118] has homology to the integrin α M and inhibits the binding of uPA to uPAR [119]. It inhibits leukocyte adhesion to fibrinogen, vitronectin, and endothelial cells.…”

Section: Inhibition Of Upa-integrin Interactionsmentioning

confidence: 99%

Role of plasminogen activator-plasmin system in tumor angiogenesis

Rakic¹,

Maillard²,

Jost³

et al. 2003

Cellular and Molecular Life Sciences (CMLS)

118

View full text Add to dashboard Cite

New blood formation or angiogenesis has become a key target in therapeutic strategies aimed at inhibiting tumor growth and other diseases associated with neovascularization. Angiogenesis is associated with important extracellular remodeling involving different proteolytic systems among which the plasminogen system plays an essential role. It belongs to the large serine proteinase family and can act directly or indirectly by activating matrix metalloproteinases or by liberating growth factors and cytokines sequestered within the extracellular matrix. Migration of endothelial cells is associated with significant upregulation of proteolysis and conversely, immunoneutralization or chemical inhibition of the system reduces angiogenesis in vitro. On the other hand genetically altered mice developed normally without overt vascular anomalies indicating the possibility of compensation by other proteases in vivo. Nevertheless, they have in some experimental settings revealed unanticipated roles for previously characterized proteinases or their inhibitors. In this review, the complex mechanisms of action of the serine proteases in pathological angiogenesis are summarized alongside possible therapeutic applications.

show abstract

“…It has been shown that uPAR acts as a high-affinity receptor for the matrix-like form of vitronectin also Wei et al, 1994;Kanse et al, 1996). This function of uPAR, together with its ability to interact with the cytoskeleton-engaged integrins (Wei et al, 1996), implicate uPAR in regulation of cell adhesion and migration, in addition to mediation of cellular signalling (Chapman, 1997).…”

mentioning

confidence: 95%

Prognostic impact of urokinase-type plasminogen activator receptor (uPAR) in cytosols and pellet extracts derived from primary breast tumours

et al. 2001

View full text Add to dashboard Cite

Summary Using a previously developed enzyme-linked immunosorbent assay (ELISA), the levels of the receptor for urokinase-type plasminogen activator (uPAR) were determined in cytosols and corresponding membrane pellets derived from 878 primary breast tumours. The levels of uPAR in the pellet extracts were more than 3-fold higher than those measured in the cytosols (P < 0.001). Moreover, the uPAR levels in the two types of extracts were weakly, though significantly, correlated with each other (r S = 0.20, P < 0.001). In Cox univariate analysis, high cytosolic levels of uPAR were significantly associated with reduced overall survival (OS) and relapse-free survival (RFS). The levels of uPAR in pellet extracts appeared not to be related with patient survival. In multivariate analysis, elevated levels of uPAR measured in cytosols and pellet extracts were found to be independent predictors of poor OS, not RFS. The prediction of poor prognosis on the basis of high uPAR levels emphasizes its important role in plasmin-mediated degradation of extracellular matrix proteins during cancer invasion and metastasis.

show abstract

Regulation of Integrin Function by the Urokinase Receptor

Cited by 701 publications

References 29 publications

Overexpression of the urokinase receptor mRNA splice variant uPAR-del4/5 affects tumor-associated processes of breast cancer cells in vitro and in vivo

Overexpression of the urokinase receptor mRNA splice variant uPAR-del4/5 affects tumor-associated processes of breast cancer cells in vitro and in vivo

Role of plasminogen activator-plasmin system in tumor angiogenesis

Prognostic impact of urokinase-type plasminogen activator receptor (uPAR) in cytosols and pellet extracts derived from primary breast tumours

Contact Info

Product

Resources

About