ABSENCE OF HOST PLASMINOGEN-ACTIVATOR INHIBITOR-1 PREVENTS CANCER INVASION AND VASCULARIZATION

Acquisition of invasive/metastatic potential through protease expressi on is an essential event in tumor progression. High levels of componen ts of the plasminogen activation system, including urokinase, but para doxically also its inhibitor, plasminogen activator inhibitor 1 (PAI1) , have been correlated with a poor prognosis for some cancers. We repo rt here that deficient PAI1 expression in host mice prevented local in vasion and tumor vascularization of transplanted malignant keratinocyt es. When this PAI1 deficiency was circumvented by intravenous injectio n 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 c ell invasion and angiogenesis.