Models for experimental metastasis were established to investigate the
influence of rmTNF on tumor-colony formation in the liver. Highly met
astatic: lymphoma tumor cells were either injected i.v. or inoculated
s.c. to form spontaneous metastases. In both systems, administration o
f rmTNF to the animals led to significant enhancement of the number of
liver metastases in comparison with control groups. The number of met
astatic tumor-cell colonies at an early stage of metastasis was increa
sed, as well as the number of surface metastases in a late stage. Cons
equently; TNF-treated animals revealed a higher mortality. The optimal
time for TNF to exert this metastasis-enhancing effect was found to b
e 7 days after tumor inoculation. In vitro adhesion of the lymphoma tu
mor cells to a mouse endothelioma cell line was strongly inhibited by
monoclonal antibodies interfering with the interaction of VCAM-1 with
VLA-4. These results support and extend earlier results with a fibrosa
rcoma lung colonization model. In addition, they show that stimulation
of the immune system in tumor-bearing hosts activates tumor-promoting
pathways, in addition to having possible beneficial effects. (C) 1995
Wiley-Liss, Inc.