Departments of Experimental Medicine and Neuroscience, University Tor Vergata, 00133 Rome, Italy.
Oncol Rep. 2010 Jul;24(1):219-23. doi: 10.3892/or_00000849.
The activity of telomerase, a ribonucleoprotein maintaining the length of chromosome ends (telomeres) to levels allowing cells to replicate indefinitely, is undetectable in normal, differentiated cells, is present at low levels in some activated cell types (including endothelial cells) and it is highly expressed by tumor cells. Kaposi's sarcoma (KS), the most frequent tumor in Acquired Immune Deficiency Syndrome (AIDS) patients (AIDS-KS), arises as a disorder of new blood vessel formation (angiogenesis), but it may evolve into an aggressive cancer, characterized by the proliferation and invasion of spindle-shaped, endothelial-like cells (KS cells, KSC). Here we report that primary KSC express low telomerase levels which are strongly enhanced by KS initiation and progression factors including the inflammatory mediators interleukin (IL)-1beta, tumor necrosis factor (TNF)alpha and interferon (IFN)gamma, the angiogenic basic fibroblast growth factor (bFGF) and the Tat protein of Human Immunodeficiency Virus (HIV)-1. Noteworthy, the increase of telomerase activity promoted by these molecules parallels the induction of KSC growth and invasion. These preliminary in vitro findings encourage measuring telomerase activity in AIDS-KS lesions in order to survey the clinical progression of the disease.
端粒酶的活性,一种维持染色体末端(端粒)长度的核糖核蛋白,使其达到允许细胞无限复制的水平,在正常分化的细胞中无法检测到,在一些激活的细胞类型(包括内皮细胞)中低水平存在,而在肿瘤细胞中高度表达。卡波济肉瘤(KS)是获得性免疫缺陷综合征(AIDS)患者中最常见的肿瘤(AIDS-KS),是一种新血管形成(血管生成)障碍,但它可能演变成侵袭性癌症,其特征是梭形、内皮样细胞(KS 细胞,KSC)的增殖和浸润。在这里,我们报告原发性 KSC 表达低水平的端粒酶,KS 起始和进展因子(包括炎症介质白细胞介素(IL)-1β、肿瘤坏死因子(TNF)α和干扰素(IFN)γ、血管生成碱性成纤维细胞生长因子(bFGF)和人类免疫缺陷病毒(HIV)-1 的 Tat 蛋白)强烈增强其表达。值得注意的是,这些分子促进的端粒酶活性的增加与 KSC 生长和浸润的诱导平行。这些初步的体外发现鼓励在 AIDS-KS 病变中测量端粒酶活性,以调查疾病的临床进展。