title: Carcinoembryonic antigen (CEA) and its receptor hnRNP M are mediators of metastasis and the inflammatory response in the liver.
abstract: This article discusses the role of carcinoembryonic antigen (CEA) as a facilitator of the inflammatory response and its effect on colorectal cancer hepatic metastasis. Colorectal cancer accounts for 11% of all cancers in the United States and the majority of deaths are associated with liver metastasis. If left untreated, median survival is only six to 12 months. Resection of liver metastases offers the only chance for cure. Of the small number of patients who have operable cancer most will have further tumor recurrence. The molecular mechanisms associated with colorectal cancer metastasis to the liver are largely unknown. However CEA production has been shown both clinically and experimentally to be a factor in an increased metastatic potential of colorectal cancers to the liver. CEA also has a role in protecting tumor cells from the effects of anoikis and this affords a selective advantage for tumor cell survival in the circulation. CEA acts in the liver through its interaction with its receptor (CEAR), a protein that is related to the hnRNP M family of RNA binding proteins. In the liver CEA binds with hnRNP M on Kupffer cells and causes activation and production of pro- and anti-inflammatory cytokines including IL-1, IL-10, IL-6 and TNF-α. These cytokines affect the up-regulation of adhesion molecules on the hepatic sinusoidal endothelium and protect the tumor cells against cytotoxicity by nitric oxide (NO) and other reactive oxygen radicals. HnRNP M signaling in Kupffer cells appears to be controlled by beta-adrenergic receptor activation. The cells will respond to the β-adrenergic receptor agonist terbutaline resulting in reduced TNF-α and increased IL-10 and IL-6 production following CEA activation. This has implications for the control of tumor cell implantation and survival in the liver.
authors: Department of Surgery, Creighton University, 2500 California Plaza, Criss III Rm 376, Omaha, NE 68178, USA. peterthomas@creighton.edu
authors: Peter
authors: P
authors: Thomas
authors: R Armour
authors: RA
authors: Forse
authors: Olga
authors: O
authors: Bajenova
mesh_terms: D000818:Animals; D002272:Carcinoembryonic Antigen / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D034761:Heterogeneous-Nuclear Ribonucleoprotein Group M / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000209:etiology* / Q000473:pathology*; D008113:Liver Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000556:secondary
chemical_list: D002272:Carcinoembryonic Antigen; D034761:Heterogeneous-Nuclear Ribonucleoprotein Group M