Identification of a carcinoembryonic antigen binding protein on monocytes

Tumor-associated monocyte/macrophage cells are important stromal components involved in tumor development. A protein on human monocyte is identified that binds to carcinoembryonic antigen (CEA), a glycoprotein overexpressed in colon tumors. This implicates a role for this protein in CEA processing and establishes a link between monocytes and colon tumor cells. In vitro uptake of 125I-labeled CEA with isolated monocytes showed time and temperature dependence. The binding of 125I-CEA was specific and saturable as it could be inhibited by an excess of unlabeled CEA. To identify the binding protein on monocyte, we used a radiolabeled photoactivable heterobifunctional crosslinking agent and demonstrated that CEA reacts with a 115kDa protein as determined by SDS-polyacrylamide gel electrophoresis and autoradiography. Treatment of human monocytes in vitro with CEA resulted in a several fold increase in the production of proinflammatory cytokines TNF-alpha, IL-1 beta, and IL-6 compared to untreated controls. Binding of CEA to the monocyte protein may have implications in colon tumorigenesis.