一种剪接形式的CD44表达前列腺癌特异性抗体F77所识别的独特聚糖。
A spliced form of CD44 expresses the unique glycan that is recognized by the prostate cancer specific antibody F77.
作者信息
Chen Xi, Nagai Yasuhiro, Zhu Zhiqiang, Ruan Hang, Peehl Donna M, Greene Mark I, Zhang Hongtao
机构信息
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Department of Urology, Stanford University School of Medicine, Stanford, CA 94305, USA.
出版信息
Oncotarget. 2017 Dec 16;9(3):3631-3640. doi: 10.18632/oncotarget.23341. eCollection 2018 Jan 9.
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.
前列腺癌是美国男性中最常见的癌症。我们实验室最初研发的单克隆抗体F77主要识别前列腺癌细胞中的糖脂以及蛋白质上的O-连接糖基化。我们已确定糖蛋白CD44的一种剪接形式是表达F77抗原的一种关键蛋白。F77特异性糖基化发生在由第14外显子编码的CD44蛋白的多个潜在糖基化位点上。CD44是一种肿瘤干细胞标志物，已知其可诱导肿瘤干性和转移。敲低CD44或FUT1基因可显著降低F77诱导的前列腺癌细胞系凋亡。我们开发了一种同时使用CD44抗体和F77的酶联免疫吸附测定法，以从前列腺癌细胞以及前列腺癌患者的血清样本中鉴定糖基化CD44的特殊形式。这些结果揭示了F77诱导肿瘤细胞凋亡的一种依赖CD44的机制，以及一种检测前列腺癌细胞分泌的糖基化CD44蛋白的新策略。
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