Molecular expression analysis of restrictive receptor for interleukin 13, a brain tumor-associated cancer/testis antigen
Molecular expression analysis of restrictive receptor for interleukin 13, a brain tumor-associated cancer/testis antigen
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DOI：
10.1007/bf03401786
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发表时间：
2000-05-01
影响因子：
5.7
通讯作者：
Gibo, DM
中科院分区：
文献类型：
--
作者：
Debinski, W;Gibo, DM
背景：绝大多数高级别胶质瘤(HGG)患者原位过度表达IL-4(IL-4)非依赖的IL-13结合部位。此外，针对胶质瘤相关部位的基于IL13的突变细胞毒素可以说是最有效的抗胶质瘤药物。已鉴定出两种IL13受体(R)蛋白：(1)IL13Rα‘，与IL3共享的异源二聚体高亲和力IL13受体；(2)IL13Rα，IL13Rα，一种不依赖IL4的单体受体。材料和方法：我们分析了IL13Rα、IL13Rα’和IL4R(β)的基因表达。研究对象为40例成人正常组织、20个中枢神经系统(CNS)离散区域、7个胎儿组织、多个培养细胞系和手术标本。结果：IL13Rα基因表达最显著的特征是其转录产物在CNS中几乎不存在。此外，只有睾丸表现出IL13Rα在外周器官中的显著表达。相反，共享的IL13/4受体的成分在中枢神经系统和重要器官如肝、心、肺和胃肠道中都很容易检测到。这些结果有力地支持了将IL13重新定向到其限制性更强的、IL4非依赖性的、用于胶质瘤诊断和治疗的受体的必要性。此外，IL13Rα的基因位于X染色体上。由于IL13Rα是(1)一种癌症相关蛋白，(2)在正常组织中几乎仅限于睾丸，(3)其基因位于X染色体上，因此IL13Rα意外地被归类为癌症/睾丸抗原。我们的发现使IL13Rα作为胶质瘤分子治疗的各种方法的靶点更具吸引力。
Background: The vast majority of patients with high-grade gliomas (HGG) over-express interleukin 4 (IL4)-independent binding sites for IL13 in situ. In addition, mutated IL13-based cytotoxins directed specifically toward glioma-associated sites are arguably the most active anti-glioma agents. Two IL13 receptor (R) proteins were identified: (1) IL13R alpha', a component of the signaling, heterodimeric high-affinity receptor for IL13 that is shared with IL3, and (2) IL13R alpha, a monomeric, IL4-independent receptor.Materials and Methods: We analyzed gene expression of IL13R alpha, IL13R alpha' and that of IL4R(beta), which is the other subunit of the shared IL13/4 receptor. The study was conducted with 40 human normal adult tissues, 20 discrete regions of the central nervous system (CNS), 7 fetal tissues, several cultured cell lines, and surgical CNS specimens.Results: The most striking feature of the IL13R alpha gene expression was the virtual lack of its transcripts within the CNS. Furthermore, only the testes exhibited a prominent presence of the mRNA for IL13R alpha among peripheral organs. In contrast, the components of the shared IL13/4 receptor were readily detected both in the CNS and in vital organs, such as liver, heart, lungs, and gastrointestinal tract.Conclusions. The results strongly support a need to redirect IL13 towards its more restrictive, IL4-independent, receptor for glioma diagnosis and therapies. Moreover, the gene for IL13R alpha resides on chromosome X. Since IL13R alpha is (1) a cancer-associated protein, (2) virtually restricted to testes among normal tissues, and (3) its gene is on chromosome X, IL13R alpha is unexpectedly categorized as a cancer/testis antigen. Our findings make IL13R alpha even more attractive as a target for variety of approaches in glioma molecular management.