Like MUC1, CEA has also been shown to play an important role in cancer cell metastasis as well as to be chemotactic for immature DCs . Neo-expression and overexpression of distinct carbohydrate epitopes on the tumor-associated CEA seems to be responsible for this effect. The degree of expression of fucosylated structures as well as the increased levels of Lewisx carbohydrate and the de novo expression of Lewisy has been associated with recognition by immature DC. Immature DCs express the specific intercellular adhesion molecule (ICAM)-3-grabbing nonintegrin (DC-SIGN) , a C-type lectin that displays high affinity for nonsialylated Lewisx and Lewisy, carbohydrate moieties found abundantly expressed on the tumor forms of CEA. Mature DCs do not interact with tumor forms of CEA, whereas immature DCs do not bind to CEA on normal cells. Besides ICAM-2 on endothelial cells  and ICAM-3 on resting T cells , which represent additional ligands for DC-SIGN, the glycosylation-dependent interaction between immature DCs and the secreted tumor cell derived CEA is suggested to play a central role in tumor tolerance through suppression of dendritic cell functions . It has also been shown in colorectal cancer that binding of CEA to Kupffer cells in the liver can stimulate the secretion of cytokines, e.g. TNF-alpha and interleukin 1-beta  that stimulate endothelial cells to increase their expression of adhesion molecules such as E-selectin. The binding of E-selectin to sialyl-Lewis antigen, carbohydrate structure on CEA and MUC1 on tumor cells, promotes tumor cell extravasation and metastasis to the liver [94, 95].
Was this article helpful?