Inhibition of colonic tumor cell growth by biliary glycoprotein

Biliary glycoproteins (BGPs) are members of the carcinoembryonic antigen (CEA) family. These glycoproteins function in vitro as intercellular adhesion molecules and, in vitro as intercellular adhesion molecules and, in the mouse, serve as receptors for the mouse hepatitis viruses. In previous studies, BGP expression has been reported to be generally downregulated in colon and liver carcinomas of human, rat and mouse origins. We now demonstrate that introduction of murine Bgp1 cDNA isoforms into a mouse colonic carcinoma cell line, negative for endogenous Bgpl expression, significantly alters the growth properties of these cells. Cells bearing two Bgp1 isoforms were growth-retarded and exhibited a reduced ability to form colonies in an in vitro transformation assay, when compared to parental or control neor cells. Furthermore, tumor formation was inhibited by 80% when cells bearing a full-length Bgp1 isoform were injected into BALB/c syngeneic mice, while cells expressing a Bgp1 isoform lacking most of the intracytoplasmic domain produced tumors as readily as the parental cells. There results indicate that a biliary glycoprotein isoform is involved in negative regulation of colonic tumor cell growth, by a process which requires its intracytoplasmic domain. The precise mechanisms causing Bgp-dependent tumor growth inhibition remain, however, to be defined.