Hepatocytes enhance Kupffer cell-mediated tumor cell cytostasis in vitro

Kupffer cells (KC) are believed to play a major role in protecting the liver from metastases. In vitro, activated KC mediate both tumor cell cytostasis and cytolysis. Because hepatocytes (HC) occupy a position adjacent to KC in vivo, we investigated the influence of HC on KC tumoricidal activity. Using an in vitro assay of KC-mediated tumor cell cytostasis against murine P815 mastocytoma cells, we found that the presence of HC in the culture profoundly increased KC tumoricidal activity. HC enhanced KC inhibition of P815 proliferation and lowered the concentration of lipopolysaccharide and interferon-gamma necessary to activate the KC to a tumoricidal state. This stimulatory HC effect was dependent on the number of HC present and was transferable in cell-free supernatants, indicating that it was mediated by a soluble secreted product of HC. Furthermore, unlike other macrophage-priming or -potentiating factors, the transferable HC factor(s) was effective only if added simultaneously with lipopolysaccharide or interferon-gamma and not effective if added before these activating agents. These data show that HC produce a soluble mediator that enhances KC tumoricidal activity, suggesting that HC and KC interactions may be critical to the antitumor defense mechanisms of the liver.