Rostami Abookheili Aliakbar, Asadi Jahanbakhsh, Khosravi Ayyoob, Gorji Ali
Department of Molecular Medicine, Faculty of Advanced Medical Technologies, Golestan University of Medical Sciences, Gorgan, Iran.
Shefa Neuroscience Research Center, Khatam Al-anbia Hospital, Tehran, Iran.
Iran J Basic Med Sci. 2024;27(8):985-995. doi: 10.22038/IJBMS.2024.74726.16228.
Esophageal cancer stem cells (ECSCs) have been identified as the subset of cells within esophageal squamous cell carcinoma that possess tumorigenic, invasive, and metastatic properties. One important aspect of cancer metastasis is the binding of sialyl-Lewis X (CD15s) with E- or P-selectin, which facilitates the adhesion and migration of cancer cells to distant sites. This study was conducted to investigate the impact of fucosylation processes on the metastatic behavior of ECSCs.
The esophageal cancer cell line (KYSE-30) was cultured and divided into control and 2F-peracetyl fucose (2F-PerAcFuc) treated groups. Spheres were harvested from these cultures. Cell invasion assay and qPCR were conducted to examine migration and marker expression in both groups. Cancer cell line-derived xenografts were established in nude mice to validate findings .
Our results initially indicated that the addition of 2F-PerAcFuc, an inhibitor of fucosylation, resulted in the down-regulation of the Fut3/CD15s pathway in both cancer stem-like cells and the xenograft model. Measurements of subcutaneous xenograft tumor volume revealed a significant decrease in tumor size among nude mice after treatment with 2F-PerAcFuc. Additionally, a reduction in Fut8/E-cadherin levels was observed in the xenograft model of nude mice. Furthermore, the administration of 2F-PerAcFuc lowered the levels of fucosylated glycoconjugates in nude mice.
Our data suggest that inhibition of fucosyltransferase 3 and 8 can reduce the metastatic capacity of cancer stem-like cells by down-regulating CD15s and E-cadherin in a mouse model of esophageal cancer.
食管癌干细胞(ECSCs)已被确定为食管鳞状细胞癌中具有致瘤、侵袭和转移特性的细胞亚群。癌症转移的一个重要方面是唾液酸化路易斯X(CD15s)与E-或P-选择素的结合,这促进癌细胞向远处部位的黏附和迁移。本研究旨在探讨岩藻糖基化过程对ECSCs转移行为的影响。
培养食管癌细胞系(KYSE-30),并分为对照组和2F-全乙酰化岩藻糖(2F-PerAcFuc)处理组。从这些培养物中收获球体。进行细胞侵袭试验和qPCR以检测两组中的迁移和标志物表达。在裸鼠中建立癌细胞系衍生的异种移植模型以验证研究结果。
我们的结果初步表明,添加岩藻糖基化抑制剂2F-PerAcFuc导致癌症干细胞样细胞和异种移植模型中Fut3/CD15s途径的下调。皮下异种移植瘤体积测量显示,用2F-PerAcFuc处理后,裸鼠的肿瘤大小显著减小。此外,在裸鼠的异种移植模型中观察到Fut8/E-钙黏蛋白水平降低。此外,给予2F-PerAcFuc降低裸鼠中岩藻糖基化糖缀合物的水平。
我们的数据表明,在食管癌小鼠模型中,抑制岩藻糖基转移酶3和8可通过下调CD15s和E-钙黏蛋白来降低癌症干细胞样细胞的转移能力。