Ciernik I F, Krayenbühl Ciernik B H, Cockerell C J, Minna J D, Gazdar A F, Carbone D P
Simmons Cancer Center, Department of Dermatology, and Department of Pathology, University of Texas, Southwestern Medical Center, Dallas, Texas 75235-8593, USA.
Clin Cancer Res. 1995 Oct;1(10):1119-24.
Several humoral growth factors may contribute to the development and growth of AIDS-associated Kaposi's sarcoma (KS). They are either provided by chronically activated cells of the immune system or in an autocrine/paracrine manner by the neoplastic cells themselves. Transforming growth factor beta(TGF-beta) may directly enhance the growth of KS cells and tumor matrix formation. To mediate a signal both TGF-beta receptors type I and type II (TbetaR-I and TbetaR-II) have to be expressed. We investigated the expression of TGF-beta, TGF-beta receptors types I and II, and endoglin, a nonsignaling-type TbetaR-III, by means of immunohistochemistry on skin biopsies from patients with AIDS-related KS. We found that the TGF-beta ligand was expressed by KS cells in 9 of 11 samples. TbetaR-II was strongly expressed in 10 of 12 samples, but none of the investigated tumor samples stained for TbetaR-I. Endoglin was weakly expressed on all KS lesions and stained the endothelium of tumor-associated vessels in 92% of the samples. These findings show that most KS lesions have the ability to produce TGF-beta and that KS cells maintain a high expression of TbetaR-II in the absence of TbetaR-I, which may allow KS to escape growth inhibitory effects of endocrine or paracrine TGF-beta.
几种体液生长因子可能在艾滋病相关卡波西肉瘤（KS）的发生和发展中起作用。它们要么由免疫系统长期激活的细胞提供，要么由肿瘤细胞自身以自分泌/旁分泌方式提供。转化生长因子β（TGF-β）可能直接促进KS细胞的生长和肿瘤基质形成。为了介导信号，I型和II型TGF-β受体（TβR-I和TβR-II）都必须表达。我们通过免疫组织化学方法研究了艾滋病相关KS患者皮肤活检组织中TGF-β、I型和II型TGF-β受体以及内皮糖蛋白（一种无信号传导功能的TβR-III）的表达情况。我们发现，在11个样本中的9个样本中，KS细胞表达TGF-β配体。在12个样本中的10个样本中，TβR-II强烈表达，但在所研究的肿瘤样本中，没有一个样本TβR-I染色阳性。内皮糖蛋白在所有KS病变中均弱表达，在92%的样本中，肿瘤相关血管内皮染色阳性。这些发现表明，大多数KS病变有能力产生TGF-β，并且KS细胞在缺乏TβR-I的情况下维持TβR-II的高表达，这可能使KS逃避内分泌或旁分泌TGF-β的生长抑制作用。
