Widespread expressions of immunoglobulin superfamily proteins in cancer cells
Widespread expressions of immunoglobulin superfamily proteins in cancer cells
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DOI：
10.1007/s00262-011-1088-1
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发表时间：
2012-01-01
影响因子：
5.8
通讯作者：
Potzold, Suzanne
中科院分区：
文献类型：
--
作者：
Lee, Gregory;Zhu, Mingang;Potzold, Suzanne
RP215 单克隆抗体 (Mab) 可识别癌细胞表达的糖蛋白的碳水化合物相关表位，称为 CA215。进行了广泛的 MALDI-TOF MS 分析来寻找 CA215 的分子身份。除了免疫球蛋白 (Ig) 重链外，还检测到与人类 T 细胞受体 (TCR) 和 Ig 样细胞粘附分子的同源性。通过RT-PCR和cDNA测序，观察到多达80%的癌细胞系显示出显着水平的TCR-α和TCR-β基因表达。选定的 Ig 样细胞粘附分子，例如 CD47、CD54、CD58 和 CD 147 在所有测试的细胞系中也高度表达。相比之下，TCR 的共受体和共刺激物（例如 CD3、CD4 和 CD8）很少表达，这表明癌细胞中 TCR 的非功能性。癌细胞系以及癌组织切片的免疫组织化学染色和蛋白质印迹测定的结果与这些观察结果一致。抗 TCR 和抗人 IgG 抗体可诱导培养癌细胞的补体依赖性细胞毒性和细胞凋亡，表明 Ig 样蛋白的表面性质。基于这些实验观察，推测这些免疫球蛋白超家族（IgSF）蛋白的表达可能与癌发生或癌症进展过程中癌细胞的免疫保护和增殖有关。表面结合的 TCR 样蛋白以及免疫球蛋白可能是基于 RP215 的抗癌药物的潜在靶点。
RP215 monoclonal antibody (Mab) was shown to recognize a carbohydrate-associated epitope of cancer cell-expressed glycoproteins, known as CA215. Extensive MALDI-TOF MS analysis was performed to search for the molecular identity of CA215. Besides immunoglobulin (Ig) heavy chains, homology to human T-cell receptors (TCR) and Ig-like cell adhesion molecules was also detected. By using RT-PCR and cDNA sequencing, it was observed that as many as 80% of cancer cell lines showed significant levels of gene expressions of TCR-alpha and TCR-beta. Selected Ig-like cell adhesion molecules such as CD47, CD54, CD58 and CD 147 were also highly expressed among all the cell lines tested. In contrast, co-receptors and co-stimulators of TCR such as CD3, CD4 and CD8 were rarely expressed demonstrating the non-functional nature of TCR in cancer cells. Results of immunohistochemical staining and Western blot assays of cancer cell lines as well as cancerous tissue sections were consistent with these observations. Anti-TCR and anti-human IgG antibodies were shown to induce complement-dependent cytotoxicity and apoptosis of cultured cancer cells indicating the surface nature of Ig-like proteins. Based on these experimental observations, it was hypothesized that the expressions of these immunoglobulin superfamily (IgSF) proteins may be relevant to the immune protection and proliferations of cancer cells during carcinogenesis or cancer progression. Surface-bound TCR-like proteins as well as immunoglobulins may be the potential targets for RP215-based anticancer drugs.