Cavallaro U, Gasparini G, Soria M R, Maier J A
Department of Biological and Technological Research (DIBIT), San Raffaele Scientific Institute, Milan, Italy.
AIDS. 1996 Sep;10(11):1211-9. doi: 10.1097/00002030-199609000-00006.
To characterize murine spindle cells isolated from Kaposi's sarcoma-like skin lesions developed in BK virus (BKV)/tat-transgenic mice.
Kaposi's sarcoma-like spindle cells isolated from the lesions were propagated in vitro, and their phenotype was investigated using a panel of antibodies against various cell markers and angiogenic factors. Immunofluorescence and Western blot techniques were used.
We observed co-expression of antigens specific for endothelial, smooth muscle and antigen-presenting cells, suggesting that cells from the TTB cell line represent poorly differentiated vascular precursors. Since TTB cells were derived from highly vascularized skin lesions, it is noteworthy that they synthesize a complex mixture of angiogenic factors, including fibroblast growth factor-2, vascular endothelial growth factor, placental growth factor, and hepatocyte growth factor. Due to their role in invasiveness and angiogenesis, we also observed the expression of urokinase plasminogen activator (uPA), uPA receptor, and plasminogen activator inhibitor-type 1 by TTB cells.
Our results suggest that TTB cells share several features with human Kaposi's sarcoma spindle cells and can be a useful in vitro system to study the molecular mechanisms involved in Kaposi's sarcoma pathogenesis. Moreover, they synthesize a complex mixture of angiogenic factors and are growth-inhibited by the anti-angiogenic drug AGM-1470.
对从BK病毒(BKV)/tat转基因小鼠发生的卡波西肉瘤样皮肤病变中分离出的小鼠纺锤体细胞进行表征。
从病变中分离出的卡波西肉瘤样纺锤体细胞在体外进行增殖,使用一组针对各种细胞标志物和血管生成因子的抗体研究其表型。采用免疫荧光和蛋白质印迹技术。
我们观察到内皮细胞、平滑肌细胞和抗原呈递细胞特异性抗原的共表达,这表明TTB细胞系的细胞代表分化程度低的血管前体细胞。由于TTB细胞来源于高度血管化的皮肤病变,值得注意的是它们合成了包括成纤维细胞生长因子-2、血管内皮生长因子、胎盘生长因子和肝细胞生长因子在内的复杂血管生成因子混合物。由于它们在侵袭和血管生成中的作用,我们还观察到TTB细胞表达尿激酶型纤溶酶原激活剂(uPA)、uPA受体和1型纤溶酶原激活剂抑制剂。
我们的结果表明,TTB细胞与人类卡波西肉瘤纺锤体细胞具有若干共同特征,可作为研究卡波西肉瘤发病机制所涉及分子机制的有用体外系统。此外,它们合成复杂的血管生成因子混合物,并被抗血管生成药物AGM-1470抑制生长。