Abstract
Metastasis is the main cause of death among colorectal cancer (CRC) patients. E-selectin and its carbohydrate ligands, including sialyl Lewis X (sLeX) antigen, are key players in the binding of circulating tumor cells to the endothelium, which is one of the major events leading to organ invasion. Nevertheless, the identity of the glycoprotein scaffolds presenting these glycans in CRC remains unclear. In this study, we firstly have characterized the glycoengineered cell line SW620 transfected with the fucosyltransferase 6 (FUT6) coding for the α1,3-fucosyltransferase 6 (FUT6), which is the main enzyme responsible for the synthesis of sLeX in CRC. The SW620FUT6 cell line expressed high levels of sLeX antigen and E-selectin ligands. Moreover, it displayed increased migration ability. E-selectin ligand glycoproteins were isolated from the SW620FUT6 cell line, identified by mass spectrometry, and validated by flow cytometry and Western blot (WB). The most prominent E-selectin ligand we identified was the neural cell adhesion molecule L1 (L1CAM). Previous studies have shown association of L1CAM with metastasis in cancer, thus the novel role as E-selectin counter-receptor contributes to understand the molecular mechanism involving L1CAM in metastasis formation.
Highlights
According to the World Health Organization, colorectal cancer (CRC) is the third most common cancer and the second cancer related cause of death worldwide, with an estimated incidence of over 1.8 million cases in 2018 [1]
Immunoprecipitated L1CAM and immunoprecipitated E-selectin ligands from SW620FUT6 membrane proteins were stained with HECA-452 and E-Ig
These results showed that L1CAM was an E-selectin ligand in SW620FUT6 cells
Summary
According to the World Health Organization, colorectal cancer (CRC) is the third most common cancer and the second cancer related cause of death worldwide, with an estimated incidence of over 1.8 million cases in 2018 [1]. The high cancer mortality is mainly due to the formation of metastasis, formed by the colonization of a distant organ or lymph nodes by tumor cells detached from the primary tumor site: this has been observed in approximately 20% of patients with CRC at first diagnosis [2,3]. Through the expression of selectin ligands and subsequent interaction with endothelial selectins, CTCs gain the ability to roll on activated endothelium. This interaction is crucial for the deceleration of the CTCs in the bloodstream. The tethering and rolling of CTCs are followed by firm adhesion via integrins allowing transendothelial migration and development of a secondary tumor, i.e., metastasis formation [8,9]
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