A mouse hepatocyte carbohydrate-specific receptor and its interaction with liver-metastasizing tumor cells

Abstract

Spontaneous high-metastatic variants (ESb) of the DBA/2 mouse lymphoma L5178Y which show heavy liver involvement were found to form rosettes in vitro with isolated autologous hepatocytes, whilst low-metastatic sublines of the same tumor (Eb) did not. An analysis of the molecules involved in the hepatocyte:tumor cell interaction was performed by affinity adsorption and SDS-polyacrylamide gel electrophoresis of 125I-labelled membrane components from either the hepatocytes or the tumor cells. The hepatocytes were found to bind ESb tumor cells through lectin-like hepatic binding proteins (HBP) with molecular weights of 52, 56 and 110 Kd and specificity for D-galactosyl and N-acetyl-D-galactosaminyl residues. More than 10 different cell surface glycoproteins of ESb tumor cells and none of Eb-type tumor cells served as ligands in the hepatocyte interaction. The low-metastatic subline Eb formed hepatocyte rosettes only after neuraminidase pretreatment, indicating that lectin binding carbohydrate structures existed in a cryptic form masked on these cells by sialic acid. Although lectin-carbohydrate interactions have been found to play a crucial role in many intercellular recognition processes, this apparently is the first molecular description of such an interaction between organ-derived normal parenchymal cells and tumor cells. The possible relevance of such an interaction for cancer metastasis is suggested by the finding that spleen-selected ESb sublines differed from liver-selected ones in their organotropism as well as in their ability to form hepatocyte rosettes.