کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2107728 | 1083697 | 2008 | 11 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Plasminogen Activator Inhibitor-1 Protects Endothelial Cells from FasL-Mediated Apoptosis Plasminogen Activator Inhibitor-1 Protects Endothelial Cells from FasL-Mediated Apoptosis](/preview/png/2107728.png)
SummaryPlasminogen 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.
Journal: - Volume 14, Issue 4, 7 October 2008, Pages 324–334