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细粒棘球绦虫中的O-糖基化:癌相关Tn抗原的鉴定与表征

O-glycosylation in Echinococcus granulosus: identification and characterization of the carcinoma-associated Tn antigen.

作者信息

Alvarez Errico D, Medeiros A, Míguez M, Casaravilla C, Malgor R, Carmona C, Nieto A, Osinaga E

机构信息

Depto. de Bioquímica, Facultad de Medicina, Montevideo, Uruguay.

出版信息

Exp Parasitol. 2001 Jun;98(2):100-9. doi: 10.1006/expr.2001.4620.

Abstract

In the present work we demonstrate that the cancer-associated O-glycosylated Tn antigen (GalNAc-O-Ser/Thr) is expressed by the cestode Echinococcus granulosus. This antigen was detected in both larval and adult worm extracts, with the highest specific activity observed in the adult excretion/secretion preparation. Histochemical analysis showed that Tn is preferentially expressed in the parenchyma in both parasite stages and the external part of tegument in adult worms. A similar pattern was observed for sialyl-Tn, a related O-linked antigen. Tn glycoproteins from protoscoleces were resolved by SDS-PAGE in two main components of 43 and 49 kDa. After purification, this material was reactive with lectins which bind GlcNAc/sialic acid, GalNAc, and T antigen. In a preliminary evaluation, high levels of Tn antigen were detected in serum samples from patients with hydatid cyst, suggesting that the measure of Tn in serum could be a biomarker of this disease, although extensive work is necessary in order to determine the clinical usefulness of this assay. The results reported here, the first evidence of O-glycosylation pathways in E. granulosus and the presence of Tn antigen in cestodes, suggest that the evaluation of O-glycosylated antigens might give new insights in the host-parasite relationship.

摘要

在本研究中,我们证明了癌症相关的O-糖基化Tn抗原(GalNAc-O-丝氨酸/苏氨酸)由绦虫细粒棘球绦虫表达。在幼虫和成虫提取物中均检测到该抗原,在成虫排泄/分泌制剂中观察到最高的比活性。组织化学分析表明,Tn在两个寄生虫阶段的实质组织以及成虫体表的外部均优先表达。对于相关的O-连接抗原唾液酸化Tn,也观察到类似的模式。原头蚴的Tn糖蛋白通过SDS-PAGE分离为43 kDa和49 kDa的两个主要成分。纯化后,该物质与结合GlcNAc/唾液酸、GalNAc和T抗原的凝集素发生反应。在初步评估中,在包虫囊肿患者的血清样本中检测到高水平的Tn抗原,这表明血清中Tn的检测可能是该疾病的生物标志物,尽管为了确定该检测方法的临床实用性还需要进行大量工作。此处报道的结果,即细粒棘球绦虫中O-糖基化途径的首个证据以及绦虫中Tn抗原的存在,表明对O-糖基化抗原的评估可能会为宿主-寄生虫关系提供新的见解。

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