A spliced form of CD44 expresses the unique glycan that is recognized by the prostate cancer specific antibody F77
A spliced form of CD44 expresses the unique glycan that is recognized by the prostate cancer specific antibody F77
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DOI：
10.18632/oncotarget.23341
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发表时间：
2018-01-09
期刊：
影响因子：
--
通讯作者：
Zhang, Hongtao
中科院分区：
文献类型：
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作者：
Chen, Xi;Nagai, Yasuhiro;Zhang, Hongtao
前列腺癌是美国男性最常见的癌症。我们实验室最初开发的单克隆抗体F77主要识别前列腺癌细胞中蛋白质上的糖脂以及O-连接的糖基化。我们已经鉴定了糖蛋白CD 44的剪接形式作为表达F77抗原的一种关键蛋白。F77特异性糖基化发生在由第十四外显子编码的CD 44蛋白上的多个潜在糖基化位点上。CD 44是一种肿瘤干细胞标志物，已知可诱导肿瘤干细胞和转移。在前列腺癌细胞系中，CD 44或FUT 1基因的敲低显著降低了F77诱导的细胞凋亡。我们使用CD 44抗体和F77开发了一种ELISA，以从前列腺癌细胞以及前列腺癌患者的血清样品中鉴定糖基化CD 44的特殊形式。这些结果揭示了F77诱导肿瘤细胞凋亡的CD 44依赖性机制，以及检测前列腺癌细胞分泌的糖基化CD 44蛋白的新策略。
Prostate cancer is the most common cancer occurring in men in the United States. The monoclonal antibody F77 that was originally developed in our laboratory recognizes mainly glycolipids as well as O-linked glycosylation on proteins in prostate cancer cells. We have identified a spliced form of glycoprotein CD44 as one critical protein expressing the F77 antigen. The F77-specific glycosylation occurs on multiple potential glycosylation sites on the CD44 protein encoded by the fourteenth exon. CD44 is a tumor stem cell marker and is known to induce tumor stemness and metastasis. Knockdown of CD44 or FUT1 genes dramatically reduced F77-induced apoptosis in prostate cancer cell lines. We developed an ELISA using both a CD44 antibody and F77 to identify the special form of glycosylated CD44 from prostate cancer cells as well as from serum samples of prostate cancer patients. These results reveal a CD44-dependent mechanism for F77 to induce tumor cell apoptosis, and a new strategy for the detection of glycosylated CD44 proteins secreted by prostate cancer cells.