Intravesical Administration of Plasminogen Activator Inhibitor Type-1 Inhibits In Vivo Bladder Tumor Invasion and Progression

Abstract

To our knowledge this study is the first to demonstrate that intravesical treatment with PAI-1 significantly inhibits tumor progression in an in vivo model of bladder cancer. Further clinical development is warranted for using PAI-1 directly or in combination with current standards, such as bacillus Calmette-Guerin or interferon.

Decrease of Plasminogen Activator Inhibitor-1 May Contribute to the Anti-Invasive Action of Cannabidiol on Human Lung Cancer Cells

“…Besides the MMP/TIMP system, the plasminogen/ plasmin system consisting of urokinase plasminogen activator (uPA), urokinase plasminogen activator receptor (uPAR) and the plasminogen activator inhibitors PAI-1 and PAI-2 has been demonstrated as an important factor in the regulation of cancer cell spreading (for review, see 24). Although high levels of PAI-1 should be intuitively beneficial in cancer by downregulating uPA proteolytic activity, apparently contradictory results have been published regarding the impact of PAI-1 on tumor invasion, angiogenesis and metastasis with studies demonstrating either inhibitory (25)(26)(27) or stimulatory effects (25,(28)(29)(30) on these events. In this context, differences in tumor models or PAI-1 concentrations as well as multiple uPA-dependent and -independent functions of PAI-1 have been suggested to contribute to the conflicting data (25).…”

Animal Models for Basic and Preclinical Research in Bladder Cancer

“…It is generally assumed that the pro-malignant effect of the uPA-uPAR system is mediated by increased local proteolysis, thus favoring tumor invasion, as well as by the pro-angiogenic effect (Binder et al, 2008). Consistent with this activity it has been shown, in a rat orthotopic model, that intravesical administration of PAI-1, which inhibits uPA activity in tumors, reduces the growth and progression of bladder cancer (Chen et al, 2009).…”

Further Understanding of Urokinase Plasminogen Activator Overexpression in Urothelial Bladder Cancer Progression, Clinical Outcomes and Potential Therapeutic Targets

“…Moreover, 22% of PAI-1 treated tumors invaded the muscle compared to 79% in the control group. 39 Development of a drug applicable in clinical trials is warranted.…”