Absence of host plasminogen activator inhibitor 1 prevents cancer invasion and vascularization.
Acquisition of invasive/metastatic potential through protease expression is an essential event in tumor progression. High levels of components of the plasminogen activation system, including urokinase, but paradoxically also its inhibitor, plasminogen activator inhibitor 1 (PAI1), have been correlated with a poor prognosis for some cancers. We report here that deficient PAI1 expression in host mice prevented local invasion and tumor vascularization of transplanted malignant keratinocytes. When this PAI1 deficiency was circumvented by intravenous injection of a replication-defective adenoviral vector expressing human PAI1, invasion and associated angiogenesis were restored. This experimental evidence demonstrates that host-produced PAI is essential for cancer cell invasion and angiogenesis.
Laboratory of Tumor and Developmental Biology, University of Liège, Belgium.
K
K
Bajou
A
A
Noël
R D
RD
Gerard
V
V
Masson
N
N
Brunner
C
C
Holst-Hansen
M
M
Skobe
N E
NE
Fusenig
P
P
Carmeliet
D
D
Collen
J M
JM
Foidart
D000256:Adenoviridae; D000818:Animals; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D018450:Disease Progression; D005260:Female; D005822:Genetic Vectors; D005838:Genotype; D006801:Humans; D015603:Keratinocytes / Q000473:pathology; D008297:Male; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis* / Q000172:deficiency* / Q000235:genetics; D012878:Skin Neoplasms / Q000098:blood supply / Q000473:pathology*; D014162:Transfection
D017395:Plasminogen Activator Inhibitor 1