Plasminogen Activator Inhibitor-1 Protects Endothelial Cells from FasL-Mediated Apoptosis.
Cancer Cell. 2008 Oct 7;14(4):324-34
Authors: Bajou K, Peng H, Laug WE, Maillard C, Noel A, Foidart JM, Martial JA, Declerck YA
Plasminogen activator inhibitor-1 (PAI-1) paradoxically enhances tumor progression and angiogenesis; however, the mechanism supporting this role is not known. Here we provide evidence that PAI-1 is essential to protect endothelial cells (ECs) from FasL-mediated apoptosis. In the absence of host-derived PAI-1, human neuroblastoma cells implanted in PAI-1-deficient mice form smaller and poorly vascularized tumors containing an increased number of apoptotic ECs. We observed that knockdown of PAI-1 in ECs enhances cell-associated plasmin activity and increases spontaneous apoptosis in vitro. We further demonstrate that plasmin cleaves FasL at Arg144-Lys145, releasing a soluble proapoptotic FasL fragment from the surface of ECs. The data provide a mechanism explaining the proangiogenic activity of PAI-1.
PMID: 18835034 [PubMed - in process]