Autologous antibody to src-homology 3-domain GRB2-like 1 specifically increases in the sera of patients with low-grade gliomas.
Autologous antibody to src-homology 3-domain GRB2-like 1 specifically increases in the sera of patients with low-grade gliomas.
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DOI：
10.1186/1756-9966-31-85
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发表时间：
2012-10-11
期刊：
影响因子：
--
通讯作者：
Iwadate Y
中科院分区：
文献类型：
--
作者：
Matsutani T;Hiwasa T;Takiguchi M;Oide T;Kunimatsu M;Saeki N;Iwadate Y
脑胶质瘤是成人最常见的原发性中枢神经系统恶性肿瘤，尽管治疗方法多种多样，但通常无法治愈。阐明早期的致癌过程对诊断和有效治疗具有重要意义。本研究采用重组cDNA表达克隆（SEREX）抗原血清学鉴定方法，探讨低级别胶质瘤中蛋白表达的细微变化。用ELISA法检测血清中抗SEREX鉴定的胶质瘤相关抗原的自身抗体水平，并使用缺失突变体和重叠肽阵列鉴定表位位点。在使用C6和9 L胶质瘤细胞系的大鼠胶质瘤模型中检查血清自身抗体水平的变化。我们通过SEREX鉴定了31种胶质瘤相关抗原。其中，低级别胶质瘤患者血清抗src同源3域GRB 2样1（SH 3GL 1）抗体水平显著高于健康志愿者和高级别胶质瘤患者。通过重叠肽阵列和使用缺失突变体的ELISA鉴定C-末端的10个氨基酸为表位位点。SH 3GL 1蛋白表达随胶质瘤进展而增加。大鼠脑胶质瘤模型证实了抗SH 3GL 1自身抗体水平在早期升高，在晚期被抑制。SH 3GL 1可能参与胶质瘤的致癌过程，并在低级别胶质瘤中有效地引发自体抗体反应。SH 3GL 1的免疫反应有助于建立一个新的诊断和治疗胶质瘤的靶点。
Glioma is the most common primary malignant central nervous system tumor in adult, and is usually not curable in spite of various therapeutic approaches. Clarification of the oncogenic process in its early stage is important for the diagnosis and effective therapy. In the present study, we used the serological identification of antigens by recombinant cDNA expression cloning (SEREX) to explore the subtle changes of the protein expression in low-grade glioma. The levels of serum autoantibodies to the SEREX-identified glioma-related antigens were analyzed by ELISA, and the epitope site was identified using deletion mutants and overlap peptide array. Changes in the serum autoantibody levels were examined in the rat glioma model using C6 and 9 L glioma cell lines. We identified 31 glioma-related antigens by SEREX. Among them, the serum level of autoantibody to src-homology 3-domain GRB2-like 1 (SH3GL1) was significantly higher in patients with low-grade glioma than healthy volunteers or high-grade gliomas. The 10 amino-acids at the C-terminal were identified as the epitope site by the overlap peptide array and the ELISA using deletion mutants. The tissue expression of SH3GL1 protein increased in proportion to glioma progression. The rat glioma models confirmed the increase of anti-SH3GL1 autoantibody level in the early stage and the suppression in the late stage. SH3GL1 may be involved in the oncogenic process of gliomas and effectively elicit an autologous antibody response in low-grade gliomas. The immunological reaction to SH3GL1 would contribute to the establishment of a novel diagnostic and therapeutic target for gliomas.
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影响因子：
64.8
作者：
ROZAKISADCOCK, M;FERNLEY, R;BOWTELL, D
通讯作者：
BOWTELL, D
影响因子：
4.4
作者：
Giachino, C;Lantelme, E;Migone, N
通讯作者：
Migone, N
影响因子：
5.7
作者：
Khalil, Ashraf A.;James, Peter
通讯作者：
James, Peter
影响因子：
6.4
作者：
Schmits, R;Cochlovius, B;Pfreundschuh, M
通讯作者：
Pfreundschuh, M
DOI：
10.1073/pnas.94.16.8569
发表时间：
1997-08-05
影响因子：
11.1
作者：
Ringstad, N;Nemoto, Y;DeCamilli, P
通讯作者：
DeCamilli, P