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 G 1 . This is the first demonstration of CEACAM1 a -4L-induced tumor suppression in liver carcinomas using a quantifiable i.p. syngeneic transplantation model.

Tumor suppressor carcinoembryonic antigen-related cell adhesion molecule 1 potentates the anchorage-independent growth of human hepatoma HepG2 cells

“…Hsieh et al reported that prostatic cancer cells transfected with CEACAM1 showed reduced anchorage-independent growth and less tumorigenicity in vivo . Laurie et al reported that enforced expression of CEACAM1-4L in a rat hepatoma cell line resulted in smaller cell aggregate size in anchorage-independent growth conditions, and delayed cell-cycle progression through the G1-S phase (Laurie et al, 2005). Although these two reports seem to contradict what we observed in our study, it should be noted that the level of indigenous CEACAM1 expression was low in the cell lines they used, in contrast to HepG2 cells which have strong CEACAM1 expression.…”

“…CEACAM1 expression was found to be decreased in HCC compared with adjacent noncancerous regions (Tanaka et al, 1997), and the loss of CEACAM1 expression adversely affected the survival of individuals with HCC (Cruz et al, 2005). Moreover, restoration of CEACAM1 expression in rat HCC cells suppressed tumorigenesis in vivo (Laurie et al, 2005), indicating that CEACAM1 is a putative tumor suppressor in HCC. However, considering the diverse role of CEACAM1 among different types of cancer cells, it is still unclear whether CEACAM1 acts only as a tumor suppressor, including during the process of HCC metastasis.…”

Signaling by epithelial members of the CEACAM family – mucosal docking sites for pathogenic bacteria

“…It is therefore not surprising, that re-expression of CEACAM1-4L in rat hepatocellular carcinoma cells results in growth suppression in vitro and reduced tumour formation in vivo [48]. In contrast, expression of CEACAM1-4S in an anchorage-dependent hepatocellular carcinoma cell line promoted robust growth of the cells in soft-agar, suggesting that CEACAM1-4S-initiated signaling rendered the cells anchorage-independent [49].…”

Cholangiocyte marker-positive and -negative fetal liver cells differ significantly in their ability to regenerate the livers of adult rats exposed to retrorsine

“…Fluorochrome-conjugated isotype antibodies of the wrong specificity (anti Fc or mu chain specific secondary antibodies with IgM or IgG primary antibodies, respectively) were used as controls. FACS was performed as previously described (Laurie et al, 2005).…”