Liver endothelial cells: Participation in host response to lymphoma metastasis

Interactions between metastasizing tumor cells and host cells in target organs determine the outcome of metastasis. This review discusses the dual role of activated host endothelial cells in the metastatic process. On one hand, the upregulation of the expression of particular adhesion molecules leads to increased tumor cell binding, and the stimulation of angiogenesis provides the vascular support for the growth of already established metastases. On the other hand, endothelial cells can contribute to host anti-metastatic responses, e.g. by production of the cytotoxic molecule nitric oxide (NO) from arginine with the help of the inducible nitric oxide synthase (iNOS). Using a well-characterized ESbL-lacZ mouse T lymphoma model with a typical three phasic growth profile, we showed during the period of growth retardation a stimulation of NO production by ex vivo isolated liver sinusoidal endothelial cells. The induction of NO synthesis in liver endothelial cells did not require the presence of Kupffer cells and appeared to be stimulated by and dependent on mature T lymphocytes. A breakdown of this NO synthesis coincided with the second tumor expansion phase.