Plasminogen activator inhibitor-1 protects endothelial cells from FasL-mediated apoptosis (Cancer Cell, 2008, 14:324-334)

報告日期: 2009/03/20
報告時間: 17:10/18:00
報告學生: 陳柏谷
講評老師: 楊倍昌
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/980320-3.pdf

Plasminogen Activator Inhibitor-1 Protects

Endothelial Cells from FasL-Mediated Apoptosis

 

Cancer Cell 14, 324–334, October 7, 2008

 

Speaker:陳柏谷

Commentator:楊倍昌 老師

Date2009/03/20

Time : 17:10-18:00

PlaceRoom 602

 

Abstract

Angiogenesis, the growth of new capillary blood vessels, is critical for development, reproduction and repair and dominates many pathological conditions. During this process, ECs become more sensitive to apoptosis through Fas/FasL pathway. ECs express and activate enzymes that degrade the ECM as they invade surrounding tissues during angiogenesis. Activated ECs produce Urokinase-type plasminogen activator (uPA), which converts plasminogen (Plg) into its active form, plasmin (Pln). Plasminogen activator inhibitor-1 (PAI-1) is the physiological inhibitor of uPA and controls the activation of plasminogen into plasmin. The two inhibitory functions of PAI-1 in proteolysis and in cell attachment initially led to the prediction that PAI-1 would have an antiangiogenic function. In previous study, in the absence of host-derived PAI-1, there is a defect of tumor vascularization in mice implanted subcutaneously with transformed keratinocytes. It is indicate that PAI-1 has a proangiogenic function, but the mechanism has remained poorly understood. In this report, author demonstrates that the increase in plasmin activity in the absence of PAI-1 might generate soluble FasL fragment and enhance Fas-dependent apoptosis. In addition, PAI-1 control of angiogenesis in vitro is Fas dependent. Therefore, these data are consistent with our data on apoptosis and indicate that PAI-1 affects angiogenesis in vitro by a mechanism that is Fas dependent.

 

References

1.    Folkman, J. (2003). Angiogenesis and apoptosis. Semin. Cancer Biol. 13, 159–167.

2.    Volpert, O.V. et., al. (2002). Inducer-stimulated Fas targets activated endothelium for destruction by anti-angiogenic thrombospondin-1 and pigment epithelium-derived factor. Nat. Med. 8, 349–357.

3.    Bajou, K., (2004). Host-derived plasminogen activator inhibitor-1 (PAI-1) concentration is critical for in vivo tumoral angiogenesis and growth. Oncogene 23, 6986–6990.