Components of the plasminogen activator system and their complexes in renal cell and bladder cancer: comparison between normal and matched cancerous tissues.
OBJECTIVE
To analyse and compare the concentration of plasminogen activator (PA), urokinase-type PA (uPA), tissue-type PA (tPA), PA inhibitor (PAI)-1 and PAI-2, and the complexes uPA-PAI-1 and tPA-PAI-1 and calculated uPA and tPA uncomplexed with PAI-1 ('free') in urothelial cell carcinoma and matched benign urothelium, and in renal cell carcinoma (RCC) and matched benign renal tissue.


METHODS
Tissue samples were obtained during cystectomy (33 patients) and nephrectomy (55), and specific enzyme-linked immunosorbent assays were used to assess the PA components in extracts of these tissues.


RESULTS
Tissue levels of uPA-PAI-1 and tPA-PAI-1, but also PAI-1 itself, were greater in tumorous bladder and kidney tissue than in matched normal tissue (by 1.5-7.8 times). Free tPA was clearly lower in tumour tissue (by 0-0.12-fold). In bladder cancer, but not in RCC, levels of uPA (15.8-fold) and free uPA (16.4-fold) were greater in tumour tissue. Free uPA levels were less in RCC (0.41-fold). For both normal bladder and kidney tissue, there was no clear correlation between uPA-PAI-1 complex and either component. However, the formation of tPA-PAI-1 complexes in normal bladder and kidney tissue was primarily determined by PAI-1. Interestingly, in tumour tissues there was a strong, significant correlation between complex levels and both components.


CONCLUSIONS
RCC and bladder cancer show distinct profiles of components of the PA system. This study provides a basis for further studies into both the (patho)physiological role of the PA system in these tumours, and into a possible relation with tumour progression and prognosis, and as target for therapy.
Span
Paul N
PN
Department of Chemical Endocrinology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. p.span@ace.umcn.nl
Witjes
Johannes A
JA
Grebenchtchikov
Nicolai
N
Geurts-Moespot
Anneke
A
Moonen
Paula M J
PM
Aalders
Tilly W
TW
Vriesema
Jessica L J
JL
Kiemeney
Lambertus A L M
LA
Schalken
Jack A
JA
Sweep
Fred C G J
FC
D014408:Biomarkers, Tumor / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000473:pathology*; D016022:Case-Control Studies; D015653:Cystectomy / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007680:Kidney Neoplasms / Q000473:pathology*; D009392:Nephrectomy / Q000379:methods; D010960:Plasminogen Activators / Q000378:metabolism*; D011379:Prognosis; D001749:Urinary Bladder Neoplasms / Q000473:pathology*; D019459:Urothelium / Q000378:metabolism / Q000473:pathology
D014408:Biomarkers, Tumor; D010960:Plasminogen Activators