P.G. Department of Studies in Biochemistry, Karnatak University, Dharwad 580 003, India.
Multidisciplinary Research Unit (MRU), Karnataka Institute of Medical Sciences, Hubli 05, India.
Int J Biol Macromol. 2024 Nov;281(Pt 4):136519. doi: 10.1016/j.ijbiomac.2024.136519. Epub 2024 Oct 12.
Metastasis-promoting Lewis and sialyl Lewis antigens expressed on glycoproteins such as mucins are frequently displayed on the surface of prostate cancer cells and could thus be ideal candidates as measures of prostate cancer aggressiveness. The current study describes the altered expression of sialyl Lewis (sLe) antigen attached to glycoproteins and key glycosyltransferases between normal prostate (RWPE-1) and cancerous cell lines (LNCaP and DU145). Our results suggest that the expression of sLe on different glycoproteins correlates with the aggressiveness of prostate cancer cells, as determined by flow cytometry and fluorescence microscopy. Blotting studies revealed that sLe-bearing glycoproteins, similar to mucins, are predominantly expressed in the more aggressive DU145 cells, followed by LNCaP cells. Immunohistochemistry technique showed a gradient of sLe expression, with low levels in low-grade prostate cancer (stage II/III) and increasing levels in high-grade cancer (stage IV), indicating its potential as a prognostic marker. Additionally, in qRT-PCR analysis significant upregulation of the glycosyltransferases GALNT5 and ST3GAL6 was observed, correlating with the increased sLe expression in LNCaP (3.2- and 14.5-fold) and DU145 (3.3- and 23.75-fold) cells. Our data indicates a correlation between sLe selectin ligand expression and prostate cancer aggressiveness. Furthermore, GALNT5 and ST3GAL6 could serve as benchmarks in PCa malignancy.
糖蛋白如黏蛋白上表达的转移促进型 Lewis 和唾液酸化 Lewis 抗原经常出现在前列腺癌细胞表面,因此可以作为评估前列腺癌侵袭性的理想候选标志物。本研究描述了正常前列腺(RWPE-1)和癌细胞系(LNCaP 和 DU145)之间黏蛋白等糖蛋白和关键糖基转移酶上唾液酸化 Lewis(sLe)抗原表达的改变。我们的结果表明,通过流式细胞术和荧光显微镜确定,不同糖蛋白上 sLe 的表达与前列腺癌细胞的侵袭性相关。印迹研究表明,与黏蛋白相似,sLe 结合的糖蛋白主要在侵袭性更强的 DU145 细胞中表达,其次是 LNCaP 细胞。免疫组织化学技术显示 sLe 表达呈梯度增加,低级别前列腺癌(II/III 期)水平较低,高级别癌症(IV 期)水平升高,表明其具有作为预后标志物的潜力。此外,在 qRT-PCR 分析中观察到糖苷转移酶 GALNT5 和 ST3GAL6 的显著上调,与 LNCaP(3.2-和 14.5 倍)和 DU145(3.3-和 23.75 倍)细胞中 sLe 表达增加相关。我们的数据表明,sLe 选择素配体表达与前列腺癌侵袭性之间存在相关性。此外,GALNT5 和 ST3GAL6 可以作为前列腺癌恶性肿瘤的基准。