The expression and functional analysis of the sialyl-T antigen in prostate cancer
The expression and functional analysis of the sialyl-T antigen in prostate cancer
复制标题
唾液酸-T抗原在前列腺癌中的表达及功能分析
DOI：
10.1007/s10719-020-09927-x
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发表时间：
2020-06-24
影响因子：
3
通讯作者：
Gao, Yin
中科院分区：
文献类型：
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作者：
Bai, Ruifeng;Luan, Xue;Gao, Yin
异常糖基化是癌症的一个特征，在癌症病理中起着重要作用；因此，了解聚糖的组成和功能对于发现癌症的诊断生物标志物和治疗靶点至关重要。在这项研究中，我们使用MALDI-TOF-MS分析来确定转移到骨（PC-3）、脑（DU145）、淋巴结（LNCaP）和椎体（VCaP）的前列腺癌细胞的theo -聚糖谱，并与来自正常前列腺组织的永生化RWPE-1细胞进行比较。前列腺癌（CaP）细胞表现出简单/短链聚糖的升高，配位聚糖的减少，多聚糖唾液化的增加和聚焦化的减少。所有CaP细胞，尤其是PC-3细胞的core1唾液酰化显著升高。α2,3-唾液基转移酶i （ST3Gal-I）产物Neu5Acα2-3Galβ1-3GalNAc-（唾液基3t抗原）的表达显著增加。因此，我们专注于探索st3gal - 1在PC-3细胞中的可能功能。ST3Gal-I沉默研究表明，ST3Gal-I与PC-3细胞增殖、迁移和凋亡相关。进一步的体内研究表明，下调ST3Gal-I可使异种移植小鼠模型的肿瘤大小减小，表明sialyl-3T可作为转移性前列腺癌预后的生物标志物，ST3Gal-I可作为癌症治疗干预的靶点。
Aberrant glycosylation is a featured characteristic of cancer and plays a role in cancer pathology; thus an understanding of the compositions and functions of glycans is critical for discovering diagnostic biomarkers and therapeutic targets for cancer. In this study, we used MALDI-TOF-MS analysis to determine theO-glycan profiles of prostate cancer cells metastasized to bone (PC-3), brain (DU145), lymph node (LNCaP), and vertebra (VCaP) in comparison to immortalized RWPE-1 cells derived from normal prostatic tissue. Prostate cancer (CaP) cells exhibited an elevation of simple/shortO-glycans, with a reduction of complexO-glycans, increasedO-glycan sialylation and decreased fucosylation. Core 1 sialylation was increased dramatically in all CaP cells, and especially in PC-3 cells. The expression of Neu5Acα2-3Galβ1-3GalNAc- (sialyl-3T antigen) which is the product of α2,3-sialyltransferase-I (ST3Gal-I) was substantially increased. We therefore focused on exploring the possible function of ST3Gal-I in PC-3 cells. ST3Gal-I silencing studies showed that ST3Gal-I was associated with PC-3 cell proliferation, migration and apoptosis. Furtherin vivostudies demonstrated that down regulation of ST3Gal-I reduced the tumor size in xenograft mouse model, indicating that sialyl-3T can serve as a biomarker for metastatic prostate cancer prognosis, and that ST3Gal-I could be a target for therapeutic intervention in cancer treatment.