Rosolen A, Todesco A, Colamonici O R, Basso G, Frascella E
Department of Pediatrics, University of Padua, Italy.
Mod Pathol. 1997 Jan;10(1):55-61.
Interferon alpha (IFN alpha) is used as an antineoplastic agent, both in hematopoietic malignancies and in solid tumors, because of its immunomodulatory action and direct antitumor activity. IFN alpha binds to specific cell-surface receptors that mediate its biologic activity. We studied the expression of IFN alpha receptors in pediatric solid tumors by use of the monoclonal antibody IFNaR3, which specifically recognizes the alpha subunit of the IFN Type I receptor. In three cell lines derived from those tumors, we determined the structure of the receptors by affinity cross-linking and immunoprecipitation techniques, and we determined their ability to mediate an antiproliferative effect. All of the tumor specimens studied by immunocytochemical analysis, including neuroblastomas, primitive neuroectodermal tumors, and rhabdomyosarcomas, stained positive for the IFN alpha receptor antibody, although in some cases immunoreactivity was weak. The three cell lines, derived from a neuroblastoma, a primitive neuroectodermal tumor, and a Ewing's sarcoma, respectively, showed the same pattern of IFN alpha receptor expression, both by affinity crosslinking and immunoprecipitation assays. Treatment with IFN alpha of those cell lines induces growth inhibition in vitro. These results suggest that IFN Type I receptor might be expressed in most solid tumors of childhood and that its structure is identical to the receptor expressed by the majority of hematologic malignancies.
α干扰素(IFNα)因其免疫调节作用和直接抗肿瘤活性,在造血系统恶性肿瘤和实体瘤中均被用作抗肿瘤药物。IFNα与介导其生物学活性的特定细胞表面受体结合。我们使用特异性识别I型干扰素受体α亚基的单克隆抗体IFNaR3,研究了儿童实体瘤中IFNα受体的表达情况。在源自这些肿瘤的三种细胞系中,我们通过亲和交联和免疫沉淀技术确定了受体的结构,并确定了它们介导抗增殖作用的能力。通过免疫细胞化学分析研究的所有肿瘤标本,包括神经母细胞瘤、原始神经外胚层肿瘤和横纹肌肉瘤,IFNα受体抗体染色均呈阳性,尽管在某些情况下免疫反应较弱。分别源自神经母细胞瘤、原始神经外胚层肿瘤和尤因肉瘤的三种细胞系,通过亲和交联和免疫沉淀试验显示出相同的IFNα受体表达模式。用IFNα处理这些细胞系可在体外诱导生长抑制。这些结果表明,I型干扰素受体可能在大多数儿童实体瘤中表达,并且其结构与大多数血液系统恶性肿瘤所表达的受体相同。