Plasminogen activator inhibitor-I and tumour growth, invasion, and metastasis.
In recent decades, evidence has been accumulating showing the important role of urokinase-type plasminogen activator (uPA) in growth, invasion, and metastasis of malignant tumours. The evidence comes from results with animal tumour models and from the observation that a high level of uPA in human tumours is associated with a poor patient prognosis. It therefore initially came as a surprise that a high tumour level of the uPA inhibitor plasminogen activator inhibitor-I (PAI-I) is also associated with a poor prognosis, the PAI-I level in fact being one of the most informative biochemical prognostic markers. We review here recent investigations into the possible tumour biological role of PAI-I, performed by animal tumour models, histological examination of human tumours, and new knowledge about the molecular interactions of PAI-I possibly underlying its tumour biological functions. The exact tumour biological functions of PAI-I remain uncertain but PAI-I seems to be multifunctional as PAI-I is expressed by multiple cell types and has multiple molecular interactions. The potential utilisation of PAI-I as a target for anti-cancer therapy depends on further mapping of these functions.
Department of Molecular Biology, University of Aarhus, 10C Gustav Wied's Vej, 8000 Aarhus C, Denmark.
Michelle K V
MK
Durand
Julie S
JS
Bødker
Anni
A
Christensen
Daniel M
DM
Dupont
Martin
M
Hansen
Jan K
JK
Jensen
Signe
S
Kjelgaard
Lisa
L
Mathiasen
Katrine E
KE
Pedersen
Sune
S
Skeldal
Troels
T
Wind
Peter A
PA
Andreasen
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000473:pathology*; D002462:Cell Membrane / Q000378:metabolism; D004195:Disease Models, Animal; D010450:Endopeptidases / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D017395:Plasminogen Activator Inhibitor 1 / Q000502:physiology*; D011379:Prognosis; D011485:Protein Binding; D011487:Protein Conformation; D019096:Vitronectin / Q000378:metabolism
D000970:Antineoplastic Agents; D017395:Plasminogen Activator Inhibitor 1; D019096:Vitronectin; D010450:Endopeptidases