Hepatocyte-tumor cell interaction in vitro. I. Conditions for rosette formation and inhibition by anti-H-2 antibody.

Abstract

In many tumor systems, the location and extent of metastases are nonrandom, suggesting that unique cell properties are important in tumor arrest and formation of secondary tumor colonies. The lung and the liver are among the most frequently involved organs. These organs are also the predominant site of metastases by tumor cells of a model system of chemically induced lymphomas in DBA/2 mice that we have been investigating (1-5). The system consists of a low-metastatic parental tumor (Eb), a spontaneous high-metastatic variant thereof (ESb), and a high-metastatic tumor line of independent origin (MDAY-D2).We previously described that ESb and MDAY-D2, but not Eb, tumor cells had the unique properties of adhesion to and invasion of normal lung tissue in vitro (1, 6). Now we describe another unique characteristic of the two metastatic tumor lines, namely, a selective binding to isolated hepatocytes in vitro.Recently Kolb et al. (7) demonstrated a lectin-like receptor on rat liver cells that has specificity for galactosyl residues and may play a role in the trapping of recirculating desialylated lymphocytes in the liver (8). In our study, we investigated whether a similar interaction might be responsible for the trapping of circulating metastatic tumor cells in the liver. Materials and MethodsTumor Cells. Eb is a Heidelberg subline of the methylcholanthrene-induced DBA/2 lymphoma L5178Y, and ESb is a spontaneous variant thereof with highly metastatic potential (1, 5). The etiology of the metastatic DBA/2 tumor MDAY-D2 has been described (9). The tumor cells were passaged in tissue culture using RPMI-1640 medium (Grand Island Biological Co., Grand Island, N. Y.) with 10% fetal calf serum (FCS) and 2 × 10 -~ M 2-mercaptoethanol, Murine Hepatocytes. Liver cell suspensions were prepared as previously described (10). An 8-12-wk-old mouse was injected with 0.3 ml of 3.6% chloral hydrate in phosphated-buffered saline and 0.1 ml of heparin (500 U/ml). The hepatic portal vein and inferior vena cava were cannulated with a 21-gauge needle and a 16-gauge plastic catheter, respectively. The liver was perfused in situ, first with perfusion buffer (10) that was saturated with 02 at 36°C for 2-3 min,

Oligosaccharide modification by swainsonine treatment inhibits pulmonary colonization by B16-F10 murine melanoma cells.

“…Treatment of cells with either glycosidases (33), lectins (33), tunicamycin (34,35), or neuraminidase (31) modulates their attachment and spreading in vitro. Recently, cell-surface lectins on normal hepatocytes that aggregate liver-metastasizing tumor cells and that may be involved in the organ selectivity of these cells have been identified (36)(37)(38). These findings support the conclusions of earlier correlative studies that linked the cell-surface protein profiles of different tumor cell sublines with their preferred organ colonization (39,40).…”

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

“…The results are shown in Table I. As reported previously (Schirrmacher et al, 1980) the low-metastatic parental line Eb did not form significant numbers of rosettes while the spontaneous high-metastatic variant ESb did. Other ESb sublines selected four times for metastasis to the liver or bone marrow also formed rosettes with the hepatocytes.…”

?Seed and soil? revisited: mechanisms of site-specific metastasis

“…In contrast, there was no difference in aggregation among any of the lines when they were allowed to aggregate with organ cells from uninvolved, nontarget tissues such as spleen and kidney (43). Comparable findings were reported in studies of a liver-colonizing lymphoma of DBA/2 mice, where the aggregation between tumor cells and hepatocytes could be inhibited by anti-H-2-antibody (44), and of an embryonal teratocarcinoma of female germ cell origin in which tumor cells adhered to monolayers established from ovarian tissue (45). In all these cases, tumors exhibiting specific patterns of metastasis either aggregated with or adhered to a mixed population of cells derived from the appropriate target organ to a significantly greater extent than they did to cells of uninvolved organs.…”