title: Carcinoembryonic antigen-related cell adhesion molecule 1a-4L suppression of rat hepatocellular carcinomas.
abstract: Carcinoembryonic antigen (CEA)-related cell adhesion molecule 1 (CEACAM1) is a member of the CEA family of immunoglobulin-like adhesion molecules with two major splice variants, CEACAM1(a)-4L and CEACAM1(b)-4S, differing in the length of their COOH-terminal cytoplasmic tail. Both forms are down-regulated in prostate and liver carcinomas relative to normal tissues. We have previously shown in a nude mouse xenograft model that restoration of CEACAM1(a)-4L expression in human prostate carcinoma cells (PC-3) suppresses tumorigenicity, an effect observed with carcinomas from several other tissues but never established for hepatocellular carcinomas. In this report, we have examined the effect of CEACAM1(a)-4L on tumorigenicity of 1682A, a rat hepatocellular carcinoma that grows on the omentum when injected into the peritoneal cavity. Results show that restoration of CEACAM1(a)-4L expression at levels 13- and 0.45-fold compared with negative controls or normal hepatocytes, respectively, completely suppressed the formation of 1682A tumor nodules on the omentum at 3 weeks after injection. In contrast, 1682A cells infected with CEACAM1(b)-4S or an empty retroviral vector formed multiple clusters of tumor nodules. Although tumor nodules of 1682A cells positive and negative for CEACAM1(a)-4L did not display significant differences in histologic organization, aggregates formed in vitro by 1682A-L were smaller in size and displayed enlarged intercellular spaces relative to their 1682A-V counterparts. Restoration of CEACAM1(a)-4L expression did not elevate levels of apoptosis but seemed to cause an increase in the length of G1. This is the first demonstration of CEACAM1(a)-4L-induced tumor suppression in liver carcinomas using a quantifiable i.p. syngeneic transplantation model.
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Rhode Island Hospital/Brown University Medical School, Providence, Rhode Island 02903, USA.
authors.forename: Nikia A
authors.initials: NA
authors.lastname: Laurie
authors.forename: Meghan M
authors.initials: MM
authors.lastname: Comegys
authors.forename: Marie P
authors.initials: MP
authors.lastname: Carreiro
authors.forename: Jeanne F
authors.initials: JF
authors.lastname: Brown
authors.forename: Donna L
authors.initials: DL
authors.lastname: Flanagan
authors.forename: Kate E
authors.initials: KE
authors.lastname: Brilliant
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Hixson
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D017209:Apoptosis / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D016193:G1 Phase / Q000502:physiology; D015870:Gene Expression; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D008114:Liver Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D020033:Protein Isoforms; D051381:Rats; D016196:S Phase / Q000502:physiology
chemical_list: D015703:Antigens, CD; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D020033:Protein Isoforms