INFLUENCE OF SPATIAL CONFIGURATION ON THE EXPRESSION OF CARCINOEMBRYONIC ANTIGEN AND MUCIN ANTIGENS IN HUMAN BLADDER-CANCER

CEA and cellular mucin antigens have been recognized as potential targ ets for specific immunotherapy and are frequently expressed in bladder cancer. We studied the coordinated expression of a bladder cancer-ass ociated CEA glycoform and of the mucins MUC1, MUC2. and MAUB under var ious growth conditions in the MGH-U3 bladder-cancer cell line, CEA and MUC2 mRNAs and proteins were detected in nude mouse tumors and sphero ids but not in monolayer cultures. Expression of MAUB and bladder-canc er CEA also was induced according to spatial configuration of cells. M UC1 was always expressed under various growth conditions, but its glyc osylation was modulated: in spheroids and mostly in tumor cells, the S M3 protein epitope was unmasked and sialyl-Tn was induced. The kinetic s of modulation of MAUB and bladder-cancer CEA were different. The epi tope recognized by the monoclonal antibody(MAb) 19A211 was rapidly ind uced in the aggregation phase of spheroid formation and rapidly lost u pon plating of tumor cells, suggesting a relationship with cell contac t. By contrast, MAUB induction in spheroids was delayed to the compact ion phase, when cell aggregates become resistant to disruption, and lo ss of expression upon tumor plating occurred slowly over several cultu re passages. No induction of these 2 antigens was observed in the pres ence of differentiation agents, endothelial cell products or interfero n-gamma, but it occurred when MGH-U3 cells were cultured at high densi ty on extracellular matrix. Our results suggest that CEA and mucin ant igen expression in bladder cancer is modulated by the spatial configur ation of cells. (C) 1997 Wiley-Liss, Inc.