Selection of a highly metastatic liver-colonizing subpopulation of Lewis lung carcinoma variant H-59 using murine hepatocyte monolayers.

ABSTRACT

We have previously described two highly metastatic variants of the Lewis lung carcinoma (3LL) with distinct patterns of organ-selective metastasis. Variant M-27 metastasizes exclusively to the lung regardless of the route of inoculation, whereas variant H-59 metastasizes primarily to the liver. The objective of this work was to investigate host-tumor cell interactions which determine the metastatic preference of these tumor cell lines. An in vitro adhesion assay using isotope-labelled tumor cells was utilized to compare the ability of the two cell lines to bind to murine hepatocytes. It was found that the proportion of H-59 cells which specifically bound to hepatocytes increased progressively for up to 30 min of incubation, at which time it peaked with as many as 30-50 per cent of the cells bound to the monolayers. The binding of M-27 cells was significantly lower and ranged from 4 to 8 per cent during incubation periods of up to 90 min. Hepatocyte monolayers were subsequently used to select a subpopulation of tumor H-59 enriched for highly adherent cells. This subpopulation was found to be highly metastatic to the liver, whereas the non-adherent fraction failed to give rise to hepatic metastases in most of the animals injected. DNA analysis using flow cytometry suggested that the selection was not based on cell-cycle related properties of the tumor cells. These results suggest that in the present tumor model, hepatic metastasis is closely related to and may be dependent on tumor cell binding to hepatocytes.