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.
Ganguly
Aniruddha
A
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
Yeltsin
Ersan
E
Robbins
Jonathan
J
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