Mebrahtu Sofia, Eriksson Ulf, Rauch Uwe, Warenholt Janina, Bendsöe Niels, Dictor Michael
Department of Pathology, Lund University Hospital, Lund, Sweden.
Exp Cell Res. 2004 Jan 15;292(2):322-31. doi: 10.1016/j.yexcr.2003.09.010.
Infection with Kaposi's sarcoma-associated herpesvirus (KSHV) is a prerequisite for Kaposi's sarcoma, a multicentric endothelial tumor of mixed blood vessel-lymphatic phenotype with a marked production of endothelial basement membrane proteins. The viral K1 gene encodes a unique transmembrane protein capable of transforming T lymphocytes experimentally. We studied the effects of K1 regulated by the endothelium-specific tie-1 promoter in the embryonic stem cell (ES)-derived endothelium of subcutaneous murine teratomas and in embryoid body cultures with and without supplemental basic fibroblast growth factor and vascular endothelial growth factor. K1 embryoid bodies showed no difference in endothelial BM protein expression, formation of basal lamina by electron microscopy or fractional area of endothelial growth in comparison with vector controls, but maturation into branching pseudovascular tubes was mildly impaired. Moreover, the marked increase in endothelial fraction induced by both growth factors in the early growth period was absent in K1 clones. Teratoma endothelium, which is partly derived from ES, showed increased proliferation and apoptosis in K1 tumors, coinciding with a possible increased tendency for microhemorrhages. K1 can thus modulate endothelial cell turnover and growth factor response, but does not alter the extracellular matrix of differentiating endothelial cells.
感染卡波西肉瘤相关疱疹病毒（KSHV）是卡波西肉瘤发生的先决条件，卡波西肉瘤是一种具有混合血管 - 淋巴管表型的多中心内皮肿瘤，能显著产生内皮基底膜蛋白。病毒K1基因编码一种独特的跨膜蛋白，该蛋白在实验中能够转化T淋巴细胞。我们研究了由内皮特异性tie-1启动子调控的K1在皮下小鼠畸胎瘤胚胎干细胞（ES）来源的内皮细胞以及有或无补充碱性成纤维细胞生长因子和血管内皮生长因子的胚状体培养物中的作用。与载体对照相比，K1胚状体在内皮基底膜蛋白表达、通过电子显微镜观察的基膜形成或内皮生长的分数面积方面没有差异，但向分支假血管管的成熟受到轻度损害。此外，在K1克隆中，早期生长阶段两种生长因子诱导的内皮分数显著增加不存在。部分源自ES的畸胎瘤内皮在K1肿瘤中显示出增殖增加和凋亡增加，这与可能增加的微出血倾向一致。因此，K1可以调节内皮细胞更新和生长因子反应，但不会改变分化内皮细胞的细胞外基质。
