A polypeptide factor produced by fibrosarcoma cells that induces endothelial tissue factor and enhances the procoagulant response to tumor necrosis factor/cachectin.
A polypeptide factor produced by fibrosarcoma cells that induces endothelial tissue factor and enhances the procoagulant response to tumor necrosis factor/cachectin.
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DOI：
10.1016/s0021-9258(19)39261-0
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发表时间：
1990-04
期刊：
影响因子：
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通讯作者：
M. Clauss;J. Murray;M. Vianna;R. D. de Waal;G. Thurston;P. Nawroth;H. Gerlach;R. Bach;P. Familletti;D. Stern
中科院分区：
文献类型：
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作者：
M. Clauss;J. Murray;M. Vianna;R. D. de Waal;G. Thurston;P. Nawroth;H. Gerlach;R. Bach;P. Familletti;D. Stern
局限于肿瘤的血管内血栓形成是血管对肿瘤坏死因子(TNF)/cachectin反应的早期组成部分。纤维蛋白与内皮细胞表面密切相关，多个微血栓形成导致肿瘤内血流量减少。我们已经确定了一种肿瘤来源的介质，它可以增强内皮促凝活性和细胞对TNF的反应，使用来自小鼠甲基胆蒽a（甲基a）诱导的纤维肉瘤的培养细胞作为模型系统。一种热稳定的蛋白酶k敏感多肽，在未还原的十二烷基硫酸钠-聚丙烯酰胺凝胶电泳中Mr约为44,000 (Mr约为56,000)，通过顺序Q-Sepharose， Mono S，反相和制备的十二烷基硫酸钠-聚丙烯酰胺凝胶电泳从甲基苯丙胺细胞的无血清培养上清中纯化约500,000倍。基于免疫学标准、生物活性和其他分子特性，甲基苯丙胺A因子似乎不同于其他细胞因子和生长因子。纯化的甲基苯丙胺A因子诱导组织因子基因的转录和促凝活性在培养的人内皮细胞中的表达（后者在大约下午6-8点达到一半的最大效果）。此外，内皮细胞与甲氧基A因子和TNF共孵育，以一种比加性更强的方式增强了组织因子的诱导。这些数据表明，某些肿瘤精心设计了一种明显独特的分子，可以改变血管壁的止血特性，潜在地调节肿瘤血管系统对宿主反应介质的反应性。
Intravascular clot formation, localized to the neoplasm, is an early component of the vascular response to tumor necrosis factor (TNF)/cachectin. Fibrin is closely associated with the endothelial cell surface, and multiple microthromboses lead to reduced blood flow in the tumor. We have identified a tumor-derived mediator which enhances endothelial procoagulant activity and the cellular response to TNF using cultured cells derived from a murine methylcholanthrene A (meth A)-induced fibrosarcoma as a model system. A heat-stable protease K-sensitive polypeptide, Mr approximately 44,000 on nonreduced sodium dodecyl sulfate-polyacrylamide gel electrophoresis (Mr approximately 56,000 reduced), was purified approximately 500,000-fold from serum-free culture supernatants of meth A cells by sequential Q-Sepharose, Mono S, reversed phase, and preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Based on immunologic criteria, biologic activity, and other molecular properties, meth A factor appears to be distinct from other cytokines and growth factors. Purified meth A factor induced transcription of the tissue factor gene and expression of procoagulant activity by cultured human endothelium (half-maximal effect for the latter at approximately 6-8 pM). Furthermore, co-incubation of endothelium with meth A factor together with TNF enhanced induction of tissue factor in a more than additive manner. These data indicate that certain tumors elaborate an apparently unique molecule which can alter hemostatic properties of the vessel wall, potentially modulating reactivity of the tumor vasculature to host response mediators.