Plasminogen activator inhibitor-1 as a measure of vascular remodelling in breast cancer

The generation of urokinase plasminogen activator (uPA) by tumours is an important pathway for neoplastic cell invasion and metastasis. Indeed in several tumour types, elevated levels of uPA, its receptor (uPAR) or its inhibitor plasminogen activator inhibitor‐1 (PAI‐1) is associated with a poorer p...

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Published in:The Journal of pathology 2001-09, Vol.195 (2), p.236-243
Main Authors: Fox, Stephen B., Taylor, Marian, Grøndahl-Hansen, Jan, Kakolyris, Stelios, Gatter, Kevin C., Harris, Adrian L.
Format: Article
Language:English
Subjects:
Adult
Aged
Biomarkers, Tumor - analysis
breast cancer
Breast Neoplasms - blood supply
Breast Neoplasms - chemistry
Breast Neoplasms - pathology
Female
Follow-Up Studies
Humans
Middle Aged
Neovascularization, Pathologic - metabolism
plasminogen activator
Plasminogen Activator Inhibitor 1 - analysis
Prognosis
Proportional Hazards Models
Receptors, Cell Surface - analysis
Receptors, Urokinase Plasminogen Activator
Survival Rate
thymidine phosphorylase
tumour angiogenesis
urokinase
Urokinase-Type Plasminogen Activator - analysis
vascular remodelling
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Summary:The generation of urokinase plasminogen activator (uPA) by tumours is an important pathway for neoplastic cell invasion and metastasis. Indeed in several tumour types, elevated levels of uPA, its receptor (uPAR) or its inhibitor plasminogen activator inhibitor‐1 (PAI‐1) is associated with a poorer prognosis. Since endothelial cells also use this proteolytic system to remodel the extracellular matrix during angiogenesis and since angiogenesis, as assessed by microvessel density, is also a predictor of patient survival, this study was designed to investigate the relationship between angiogenesis and the urokinase system in breast tumours. The aims were to assess whether the uPA, uPAR and/or PAI‐1 correlates with angiogenic activity and could therefore be a useful objective clinical measure of tumour neovascularization; and to clarify whether the poor outcome associated with high levels of the urokinase system is due to its association with angiogenesis. The study also sought to examine the relationship between the uPA system and vessel remodelling using loss of a basement membrane epitope (LH39) normally associated with established capillaries. The cytosolic levels of uPA, PAI‐1 and uPAR were therefore measured by enzyme linked immunoabsorbent assay, together with tumour vascularity, in 136 well‐characterized invasive breast carcinomas. There were significant relationships between uPA and uPAR (Spearman r=0.37, p
ISSN:0022-3417
1096-9896
DOI:10.1002/path.931