Fucosyltransferase ۳ and ۸ promote the metastatic capacity of cancer stem-like cells via CD۱۵s and E-cadherin in esophageal cancer

Objective(s): 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 (CD۱۵s) 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.Materials and Methods: The esophageal cancer cell line (KYSE-۳۰) was cultured and divided into control and ۲F-peracetyl fucose (۲F-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 in vivo.Results: Our results initially indicated that the addition of ۲F-PerAcFuc, an inhibitor of fucosylation, resulted in the down-regulation of the Fut۳/CD۱۵s 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 ۲F-PerAcFuc. Additionally, a reduction in Fut۸/E-cadherin levels was observed in the xenograft model of nude mice. Furthermore, the administration of ۲F-PerAcFuc lowered the levels of fucosylated glycoconjugates in nude mice.Conclusion: Our data suggest that inhibition of fucosyltransferase ۳ and ۸ can reduce the metastatic capacity of cancer stem-like cells by down-regulating CD۱۵s and E-cadherin in a mouse model of esophageal cancer.

Keywords:

E-cadherin , Esophageal cancer stem - cells , ۲F-PerAcFuc , Fucosyltransferase ۳ and ۸ , Sialyl lewis X