Tumors which grew out from threshold s.c. inocula of L5178Y-F9 and SL2-5 murine
T-cell lymphomas in syngeneic DBA/2 mice exhibited a unified natural defense-resistant phenotype including an increased tumorigenicity and correlating reductions in susceptibility to natural
antibodies, natural killer cells, and activated macrophages in vitro. The metastatic potential and cell surface saccharide expression of these cells were determined to assess the impact of growth from a small
tumor focus in vivo on subsequent metastatic ability and to determine whether there was any association with changes in cell surface
carbohydrates, which have been implicated now for many years in
tumor development. A significantly increased liver-colonizing ability was observed following i.v. injection. The most consistent change in cell surface saccharide expression detected in studies using five
lectins was an increase in
N-acetyl-D-galactosamine (D-GalNAc)-specific
soybean agglutinin (SBA) binding. The log of experimental liver
metastasis, SBA binding, and the percentage of hepatocyte rosetting of the parental and in vivo-selected cells exhibited significant direct correlations. While inhibition of rosetting with in vivo-selected lines by D-GalNAc and
galactose was consistent with the involvement of the
D-galactose/D-GalNAc-specific hepatocyte receptor, preincubation of the
tumor cells but not hepatocytes with D-GalNAc inhibited hepatocyte rosetting and D-GalNAc inhibited homotypic
tumor cell binding. These data suggest a role for a saccharide-specific,
lectin-like receptor on
tumor cells in both interactions and therefore in the increased experimental liver
metastasis. Furthermore, the increased expression of D-GalNAc-inhibitable SBA binding sites on the in vivo-selected variants should increase the homotypic binding by the D-GalNAc-specific
lectin-like receptors on the
tumor cells providing a rationale for the direct relationship observed between increased SBA binding and i.v. metastatic potential.