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The expression and functional analysis of the sialyl-T antigen in prostate cancer.
Glycoconjugate Journal ( IF 3 ) Pub Date : 2020-06-24 , DOI: 10.1007/s10719-020-09927-x
Ruifeng Bai 1 , Xue Luan 1 , Yu Zhang 1 , Catherine Robbe-Masselot 2 , Inka Brockhausen 3 , Yin Gao 1, 3
Affiliation  

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 the O-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/short O-glycans, with a reduction of complex O-glycans, increased O-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. Further in vivo studies 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.

中文翻译:

唾液酸-T抗原在前列腺癌中的表达和功能分析。

异常糖基化是癌症的特征,并在癌症病理中起作用。因此,了解聚糖的组成和功能对于发现癌症的诊断性生物标志物和治疗靶标至关重要。在这项研究中,我们使用MALDI-TOF-MS分析来确定转移至骨(PC-3),脑(DU145),淋巴结(LNCaP)和椎骨(VCaP)的前列腺癌细胞的O-聚糖谱来源于正常前列腺组织的永生化RWPE-1细胞。前列腺癌(CAP)细胞表现出简单/短的正视ö -glycans,具有减少复杂的ø -glycans,增加ö-聚糖唾液酸化和岩藻糖基化降低。在所有CaP细胞中,尤其是在PC-3细胞中,核心1唾液酸化作用均显着增加。α2,3-唾液酸转移酶-1(ST3Gal-1)的产物Neu5Acα2-3Galβ1-3GalNAc-(唾液酸-3T抗原)的表达显着增加。因此,我们集中于探索ST3Gal-1在PC-3细胞中的可能功能。ST3Gal-1的沉默研究表明ST3Gal-1与PC-3细胞的增殖,迁移和凋亡相关。进一步的体内研究表明,ST3Gal-1的下调降低了异种移植小鼠模型中的肿瘤大小,表明sialyl-3T可以作为转移性前列腺癌预后的生物标志物,并且ST3Gal-1可以作为治疗性干预的靶点。癌症治疗。
更新日期:2020-06-24
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