Varricchio F, Husain S R, Leland P, Gill P, Puri R K
Division of Biostatistics and Epidemiology, Center for Biologics Evaluation and Research, FDA, Rockville, MD, USA.
Oncol Res. 1997;9(9):495-503.
We have investigated the expression of interleukin-4 receptors (IL-4R) in acquired immunodeficiency syndrome (AIDS)-related Kaposi's Sarcoma (KS) in situ by immunohistochemistry. Frozen and fixed sections from five patch stage and two nodular stage KS lesions were stained with anti-IL-4R monoclonal antibody with similar results. Skin biopsies from the clinically apparent lesions and adjacent clinically uninvolved skin were also examined. We observed that individual KS cells lining the irregular vascular spaces were stained with anti-IL-4R antibody, although the degree of staining was variable. The epithelioid and oval cells appear to stain more than the spindle cells in plaque stages or nodular lesions. The sections from nonclinically involved skin also contained a few cells with features of KS, singly or in clusters that also stained for IL-4R. Skin sections from four normal donors did not stain with IL-4R antibody except for hair follicles, sweat glands, and faint staining of blood vessels. KS sections were also stained with antibodies to basic fibroblast growth factor (FGF), S100, fibronectin, and von Willebrand factor. KS lesions from clinically involved and uninvolved skin sections were positive for all four antibodies. Thus, the differences between KS lesion and clinically uninvolved skin adjacent to a KS lesion may be more quantitative than qualitative. The IL-4 receptors on KS cells were functional as IL-4 modulated intercellular adhesion molecule 1 (ICAM-1) on these cells. Taken together, our results suggest that AIDS-KS cells express elevated levels of IL-4R compared to normal endothelial and skin cells and, thus, the receptors for IL-4 on KS may serve as an attractive target for anticancer therapy.
我们通过免疫组织化学方法研究了白细胞介素-4受体（IL-4R）在获得性免疫缺陷综合征（AIDS）相关卡波西肉瘤（KS）原位的表达情况。对5个斑块期和2个结节期KS病变的冰冻切片和固定切片用抗IL-4R单克隆抗体进行染色，结果相似。还检查了临床明显病变处及相邻临床未受累皮肤的皮肤活检标本。我们观察到，内衬不规则血管腔隙的单个KS细胞被抗IL-4R抗体染色，尽管染色程度有所不同。在斑块期或结节性病变中，上皮样细胞和椭圆形细胞的染色似乎比梭形细胞更多。来自临床未受累皮肤的切片中也含有一些具有KS特征的单个或成簇细胞，这些细胞也对IL-4R染色。来自4名正常供体的皮肤切片除毛囊、汗腺和血管有微弱染色外，未被IL-4R抗体染色。KS切片还用碱性成纤维细胞生长因子（FGF）抗体、S100、纤连蛋白和血管性血友病因子抗体进行了染色。临床受累和未受累皮肤切片的KS病变对所有这四种抗体均呈阳性。因此，KS病变与KS病变相邻的临床未受累皮肤之间的差异可能更多是数量上的而非质量上的。KS细胞上的IL-4受体具有功能，因为IL-4可调节这些细胞上的细胞间黏附分子1（ICAM-1）。综上所述，我们的结果表明，与正常内皮细胞和皮肤细胞相比，AIDS-KS细胞表达升高水平的IL-4R，因此，KS上的IL-4受体可能是抗癌治疗的一个有吸引力的靶点。
