A MUC1 mucin secreted from a colon carcinoma cell line inhibits target cell lysis by natural killer cells.

The effect of two secreted mucin-type glycoproteins on natural killer (NK) cell cytotoxicity against K562 target cells has been studied. These mucins carry the carcinoma-associated sialyl-Lewis a carbohydrate epitopes and were purified from the human colon adenocarcinoma cell line COLO 205 secretions, where they lack their cytoplasmic parts. The larger one has an apoprotein encoded by the MUC1 gene, and the smaller one has CD43 (leukosialin) as the core protein. The purified MUC1 mucin could inhibit the target cell lysis by NK cells in a dose-response-dependent way, whereas other mucin domains of similar size showed no inhibition. The second mucin, CD43, inhibited lysis by NK cells, although less than the larger one. The MUC1 mucin bound to the enriched natural killer cell preparations in a partial Ca2+-dependent way as well. This mucin also bound to the target cells. The K562 cells, normally expressing high amount of CD43, showed an increased resistance to lysis by NK cells when transfected with MUC1 cDNA compared with nontransfected cells. One can speculate that mucins secreted or expressed in the plasma membrane of cancer cells could interfere with NK cell-mediated lysis.