INHIBITION OF COLONIC TUMOR-CELL GROWTH BY BILIARY GLYCOPROTEIN

Biliary glycoproteins (BGPs) are members of the carcinoembryonic antig en (CEA) family, These glycoproteins function in vitro as intercellula r adhesion molecules and, in the mouse, serve as receptors for the mou se hepatitis viruses, In previous studies, BGP expression has been rep orted to be generally downregulated in colon and liver carcinomas of h uman, rat and mouse origins, We now demonstrate that introduction of m urine Bgp1 cDNA isoforms into a mouse colonic carcinoma cell line, neg ative for endogenous Bgpl expression, significantly alters the growth properties of these cells, Cells bearing two Bgpl isoforms were growth -retarded and exhibited a reduced ability to form colonies in an ill v itro transformation assay, when compared to parental or control neo(r) cells, Furthermore, tumor formation was inhibited by 80% when cells b earing a full-length Bgpl isoform were injected into BALB/c syngeneic mice, while cells expressing a Bgpl isoform lacking most of the intrac ytoplasmic domain produced tumors as readily as the parental cells, Th ese results indicate that a biliary glycoprotein isoform is involved i n 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.