Carcinoembryonic antigen-related cell adhesion molecule 1a-4L suppression of rat hepatocellular carcinomas

• Published in: Cancer research (Chicago, Ill.) Ill.), 2005-12, Vol.65 (23), p.11010-11017
• Main Authors: LAURIE, Nikia A, COMEGYS, Meghan M, CARREIRO, Marie P, BROWN, Jeanne F, FLANAGAN, Donna L, BRILLIANT, Kate E, HIXSON, Douglas C
• Format: Article
• Language: English
• Subjects: Animals; Antigens, CD - biosynthesis; Antigens, CD - genetics; Antigens, CD - physiology; Apoptosis - physiology; Biological and medical sciences; Cell Adhesion Molecules - biosynthesis; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - physiology; Cell Growth Processes - physiology; Cell Line, Tumor; G1 Phase - physiology; Gastroenterology. Liver. Pancreas. Abdomen; Gene Expression; Hepatocytes - cytology; Hepatocytes - metabolism; Hepatocytes - physiology; Liver Neoplasms, Experimental - genetics; Liver Neoplasms, Experimental - metabolism; Liver Neoplasms, Experimental - pathology; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Medical sciences; Protein Isoforms; Rats; S Phase - physiology; Tumors
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-04-2841

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.