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. The se mucins carry the carcinoma-associated sialyl-Lewis a carbohydrate e pitopes and were purified from the human colon adenocarcinoma cell lin e COLO 205 secretions, where they lack their cytoplasmic parts, The la rger one has an apoprotein encoded by the MUC1 gene, and the smaller o ne has CD43 (leukosialin) as the core protein, The purified MUC1 mucin could inhibit the target cell lysis by NK cells in a dose-response-de pendent way, whereas other mucin domains of similar size showed no inh ibition. The second mucin, CD43, inhibited lysis by NK cells, although less than the larger one. The MUC1 mucin bound to the enriched natura l killer cell preparations in a partial Ca2+-dependent way as well, Th is mucin also bound to the target cells, The K562 cells, normally expr essing 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 pla sma membrane of cancer cells could interfere with NK cell-mediated lys is. (C) 1997 Academic Press.