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.
Laboratory of Cancer Biology, Department of Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA. aniruddha_ganguly@hms.harvard.edu
Aniruddha
A
Ganguly
Ersan
E
Yeltsin
Jonathan
J
Robbins
D002272:Carcinoembryonic Antigen / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D006801:Humans; D008970:Molecular Weight; D009000:Monocytes / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding; D011956:Receptors, Cell Surface
D002272:Carcinoembryonic Antigen; D002352:Carrier Proteins; D016207:Cytokines; D011956:Receptors, Cell Surface; C065686:carcinoembryonic antigen binding protein, human