[PDF][PDF] Plasminogen activator inhibitor-1 protects endothelial cells from FasL-mediated apoptosis

K Bajou, H Peng, WE Laug, C Maillard, A Noel… - Cancer cell, 2008 - cell.com
K Bajou, H Peng, WE Laug, C Maillard, A Noel, JM Foidart, JA Martial, YA DeClerck
Cancer cell, 2008cell.com
Summary 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 …
Summary
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.
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