Journal ArticleDOI
The urokinase plasminogen activator system: role in malignancy.
Reads0
Chats0
TLDR
Assay of uPA and PAI-1 may help identify low risk node-negative patients for whom adjuvant chemotherapy is unnecessary, and preclinical studies show that either inhibition of u PA catalytic activity or prevention of UPA binding to its receptor reduces tumor growth, angiogenesis and metastasis.Abstract:
The urokinase plasminogen activator (uPA) system consists of the serine protease uPA, its glycolipid-anchored receptor, uPAR and its 2 serpin inhibitors, plasminogen activator inhibitor-1 (PAI-1) and plasminogen activator inhibitor-2 (PAI-2). Recent findings suggest that the uPA system is causally involved at multiple steps in cancer progression. In particular, uPA has been implicated in remodelling of the extracellular matrix, enhancing both cell proliferation and migration and modulating cell adhesion. Consistent with its role in cancer progression, multiple groups have shown that high levels of uPA in primary breast cancers are independently associated with adverse outcome. Paradoxically, high levels of PAI-1 also correlate with poor prognosis in patients with breast cancer. The prognostic value of uPA/PAI-1 in axillary node-negative breast cancer patients was recently validated using both a prospective randomised trial and a pooled analysis, i.e., in 2 different Level 1 Evidence studies. Assay of uPA and PAI-1 may thus help identify low risk node-negative patients for whom adjuvant chemotherapy is unnecessary. Finally, preclinical studies show that either inhibition of uPA catalytic activity or prevention of uPA binding to its receptor reduces tumor growth, angiogenesis and metastasis.read more
Citations
More filters
Journal ArticleDOI
Metastasis: recent discoveries and novel treatment strategies
Suzanne A. Eccles,Danny R. Welch +1 more
TL;DR: This work focuses on recent findings regarding intrinsic and extrinsic molecular mechanisms controlling metastasis that determine how, when, and where cancers metastasise, and their implications for patient management in the 21st century.
Journal ArticleDOI
Vascular endothelial growth factor (VEGF) signaling in tumor progression
TL;DR: Owing to the importance of angiogenesis in tumor progression, inhibition of VEGF signaling represents an attractive cancer treatment.
Journal ArticleDOI
Cancer invasion and metastasis: changing views†
TL;DR: Recent advances in molecular and clinical aspects of metastasis are reviewed to lead to the development of new molecular markers for predicting the likely formation of metastases as well as the identification of new targets for anti‐metastatic therapies.
Journal ArticleDOI
Pleiotropic functions of plasminogen activator inhibitor-1.
TL;DR: Studies with transgenic mice have revealed a functional role for PAI‐1 in wound healing, atherosclerosis, metabolic disturbances such as obesity and insulin resistance, tumor angiogenesis, chronic stress, bone remodeling, asthma, rheumatoid arthritis, fibrosis, glomerulonephritis and sepsis.
Journal ArticleDOI
CD95 ligand induces motility and invasiveness of apoptosis-resistant tumor cells.
Bryan C. Barnhart,Patrick Legembre,Eric M. Pietras,Concetta Bubici,Guido Franzoso,Marcus E. Peter +5 more
TL;DR: The data suggest that CD95L, which is found elevated in many human cancer patients, has tumorigenic activities on human cancer cells, and could become highly relevant during chemotherapy, which can cause upregulation of CD95 ligand by both tumor and nontumor cells.
Related Papers (5)
Pooled analysis of prognostic impact of urokinase-type plasminogen activator and its inhibitor PAI-1 in 8377 breast cancer patients.
Maxime P. Look,Wim L. J. van Putten,Michael J. Duffy,Nadia Harbeck,Ib Jarle Christensen,Christoph Thomssen,Ronald E. Kates,Frédérique Spyratos,Mårten Fernö,Serenella Eppenberger-Castori,C. G. J. Fred Sweep,Kurt Ulm,J. P. Peyrat,Pierre-Marie Martin,Henri Magdelenat,Nils Brünner,Catherine Duggan,Björn W. Lisboa,Pär-Ola Bendahl,Véronique Quillien,A Daver,Gabriel Ricolleau,Marion E. Meijer-van Gelder,Peggy Manders,W. Edward Fiets,Marinus A. Blankenstein,Philippe Broët,Sylvie Romain,Günter Daxenbichler,Gudrun Windbichler,Tanja Cufer,Simona Borštnar,Willy Kueng,Louk V.A.M. Beex,Jan G. M. Klijn,Niall O'Higgins,Urs Eppenberger,Fritz Jänicke,Manfred Schmitt,John A. Foekens +39 more