COLON-CARCINOMA CELLS BLOCKED IN POLARIZATION EXHIBIT INCREASED EXPRESSION OF CARCINOEMBRYONIC ANTIGEN

Carcinoembryonic antigen (CEA) is an oncofetal protein whose regulatio n is poorly understood, although CEA is commonly expressed on many car cinoma cell types and enhances experimental metastases. The abundance of membrane-associated CEA was increased 3-fold when HD6 colon carcino ma cells were prevented from polarizing by culture for 3 days in low c alcium medium. Polarization is an early event in HD6 cell differentiat ion, with the polarized cells forming a tight, laterally adherent mono layer by culture in normal calcium medium. Lateral adherence can occur because 3 days of culture in normal calcium medium increases expressi on of calcium-dependent intercellular adhesion proteins: a 35-fold inc rease in membrane abundance of LCAM and a 16-fold increase in membrane abundance of the desmosomal protein desmoglein 1. Polarized HD6 cells exhibit low levels of CEA only at their apical luminal surface. Round ed, unpolarized HD6 cells do not exhibit increases in either LCAM or d esmoglein I membrane expression, but express increased levels of CEA m olecules throughout their cell surface, where they act as intercellula r adhesion molecules, allowing unpolarized cells to form random cell t o cell contacts. Cells cultured in low calcium medium form calcium-ind ependent cell aggregates whose formation can be blocked by Fab' fragme nts of anti-CEA monoclonal antibody col-1. The familiar pattern of ran dom, multilayered associations of tumor cells both in vitro and in xen ographs in vivo may be due to intercellular adhesion mediated by CEA w hich is up-regulated and expressed throughout the cell surface of unpo larized tumor cells.