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‐car‐bohydrate 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.