Anomalous expression of Thy1 (CD90) in B-cell lymphoma cells and proliferation inhibition by anti-Thy1 antibody treatment
Anomalous expression of Thy1 (CD90) in B-cell lymphoma cells and proliferation inhibition by anti-Thy1 antibody treatment
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DOI：
10.1016/j.bbrc.2010.04.092
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发表时间：
2010-05-28
影响因子：
3.1
通讯作者：
Honke, Koichi
中科院分区：
文献类型：
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作者：
Ishiura, Yoshihito;Kotani, Norihiro;Honke, Koichi
抗CD20单克隆抗体（Ab）利妥昔单抗被认为是治疗恶性B细胞淋巴瘤的有效抗体；然而，选择抗体药物需要发现其他细胞表面抗原。考虑到许多肿瘤相关抗原是聚糖，我们在糖缀合物中寻找治疗性抗体靶向的候选抗原。为此，我们首先关注伯基特淋巴瘤细胞系 Akata 感染 Epstein-Barr 病毒 (EBV) 时糖原表达的差异。利用DNA阵列、流式细胞术和Western blotting，我们发现Thy1在EBV阳性Akata细胞中高表达。随后。 Thy1 被发现在其他 B 细胞淋巴瘤细胞系中表达：BJAB、MutuI 和 MutuIII，与 EBV 感染无关。用抗 Thy1 单克隆抗体处理这些细胞比治疗性 Ab rituximab 更能抑制增殖。 B细胞淋巴瘤细胞系根据增殖抑制程度进行分类，与Thy1的表达水平无关。研究表明，受体酪氨酸激酶在脂筏中的稳定驻留维持了 B 细胞淋巴瘤细胞的生长。 (C) 2010 Elsevier Inc. 保留所有权利。
The anti-CD20 monoclonal antibody (Ab) rituximab is accepted to be an effective therapeutic Ab for malignant B-cell lymphoma; however, discovery of other cell surface antigens is required for the option of antibody medicine. Considering that many tumor-associated antigens are glycans, we have searched glycoconjugates for the candidate antigens that therapeutic Abs target. To this end, we first focused on the difference in the glycogenes expression in terms of Epstein-Barr virus (EBV) infection of a Burkitt's lymphoma cell line, Akata. Using DNA array, flow cytometry and Western blotting, we found that Thy1 was highly expressed in EBV-positive Akata cells. Subsequently. Thy1 was found to be expressed in other B-cell lymphoma cell lines: BJAB, MutuI, and MutuIII, irrespective of EBV infection. Treatment of these cells with an anti-Thy1 monoclonal antibody inhibited proliferation more strongly than the therapeutic Ab rituximab. The B-cell lymphoma cell lines were classified based on the extent of the proliferation inhibition, which was not correlated with the expression level of Thy1. It is suggested that stable residence of receptor tyrosine kinases in lipid rafts sustains cell growth in B-cell lymphoma cells. (C) 2010 Elsevier Inc. All rights reserved.