Tumor defense systems using O-glycans

During the process of hematogenous tumor metastasis, tumor cells that dissociated from the primary site enter the blood vessels and are exposed to innate immune systems in host blood circulation. In the innate immune systems, natural killer (NK) cells play a major role in rejecting tumors and suppressing metastasis. To establish metastasis, tumor cells therefore need to defend themselves against tumor rejection by NK cells. It has been recently discovered that some tumor cells develop defense systems against NK cell attack using certain types of cell-surface carbohydrates. The types of carbohydrates attached to cell-surface glycoproteins through serine or threonine residues contain a branch consisting of β-1,6-linkage of N-acetylglucosamine and N-acetylgalactosamine and are designated as core2 O-glycans. Tumor cells expressing core2 O-glycans evade NK cell-mediated tumor rejection, thereby surviving longer in host circulation and acquiring high-metastatic phenotypes. This review explains two types of tumor defense systems against NK cell immunity using core2 O-glycans.