Department of Biochemistry, Kochi University Medical School, Kohasu, Okocho, Nankoku, Kochi 783-8505, Japan.
Biochem Biophys Res Commun. 2010 May 28;396(2):329-34. doi: 10.1016/j.bbrc.2010.04.092. Epub 2010 Apr 18.
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.
抗 CD20 单克隆抗体（Ab）利妥昔单抗被认为是治疗恶性 B 细胞淋巴瘤的有效治疗性 Ab；然而，需要发现其他细胞表面抗原以选择抗体药物。鉴于许多肿瘤相关抗原是糖，我们一直在寻找糖缀合物作为治疗性 Ab 靶向的候选抗原。为此，我们首先关注 EBV 感染的 Burkitt 淋巴瘤细胞系 Akata 中糖基因表达的差异。使用 DNA 微阵列、流式细胞术和 Western blot，我们发现 Thy1 在 EBV 阳性的 Akata 细胞中高度表达。随后，发现 Thy1 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可更强烈地抑制增殖，比治疗性 Ab 利妥昔单抗更强。根据增殖抑制的程度对 B 细胞淋巴瘤细胞系进行分类，与 Thy1 的表达水平无关。提示受体酪氨酸激酶在脂筏中的稳定存在维持了 B 细胞淋巴瘤细胞的生长。
