Polyoma middle T-induced vascular tumor formation: The role of the plasminogen activator plasmin system

被引:58
作者
Sabapathy, KT
Pepper, MS
Kiefer, F
MohleSteinlein, U
TacchiniCottier, F
Fetka, I
Breier, G
Risau, W
Carmeliet, P
Montesano, R
Wagner, EF
机构
[1] UNIV VIENNA,RES INST MOL PATHOL,A-1030 VIENNA,AUSTRIA
[2] ONTARIO CANC INST,TORONTO,ON M4X 1K9,CANADA
[3] UNIV GENEVA,MED CTR,DEPT PATHOL,CH-1211 GENEVA 4,SWITZERLAND
[4] MAX PLANCK INST PHYSIOL & CLIN RES,DEPT MOL & CELL BIOL,D-61231 BAD NAUHEIM,GERMANY
[5] FLANDERS INTERUNIV INST BIOTECHNOL,CTR TRANSGENE TECHNOL & GENE THERAPY,B-3000 LOUVAIN,BELGIUM
关键词
D O I
10.1083/jcb.137.4.953
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The middle T antigen of murine Polyomavirus (PymT) rapidly transforms endothelial cells, leading to the formation of vascular tumors in newborn mice, Transformed endothelial (End.) cell lines established from such tumors exhibit altered proteolytic activity as a result of increased expression of urokinase-type plasminogen activator (uPA) and are capable of inducing vascular tumors efficiently when injected into adult mice, In this study we have used mice lacking components of the PA/plasmin system to analyze the role of this system in the transformation process and in tumor growth, We found that the proteolytic status of the host is not a critical determinant for PymT-induced vascular tumor formation. In addition, the lack of either uPA or tissue-type PA (tPA) activity is not limiting for the establishment and proliferation of End, cells in vitro, although the combined loss of both PA activities leads to a marked reduction in proliferation rates, Furthermore, the in vitro morphogenetic properties of mutant End, cells in fibrin gels could only be correlated with an altered proteolytic status in cells lacking both uPA and tPA. However, in contrast with tumors induced by PymT itself, the tumorigenic potential of mutant and wild-type End, cell lines was found to be highly dependent on the proteolytic status of both the tumor cells and the host. Thus, genetic alterations in the PA/plasmin system affect vascular tumor development, indicating that this system is a causal component in PymT-mediated oncogenesis.
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页码:953 / 963
页数:11
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