The importance of 5-HT for tumor cell lodgement in the liver

Arrest and lodgement of circulating tumor cells in the microvasculature is a prerequisite for metastasis formation. Aggregation of activated platelets and subsequent release of bioactive substances seem to influence the lodgement process. Since thrombocytopenia has been shown to reduce lodgement and since 5-HT is one of the compounds released from activated platelets, the present investigation was directed toward the influence of this amine on tumor cell lodgement in the liver after intraportal injection of fibrosarcoma cells. Lodgement was quantitated by an isotope technique with simultaneous measurements of 5-HT levels by a LCEC technique in rat liver biopsies from areas with lodged tumor cells as observed with vital fluorescence microscopy. To test the importance of 5-HT released from platelets, thrombocytopenia was induced with anti-platelet serum in one experimental group, while animals in another group were treated with ketanserin (a selective 5-HT2 receptor blocking agent). Animals given tumor cells alone showed a two-fold increase in 5-HT levels compared with animals injected with saline, indicating a relation between 5-HT release and tumor cell lodgement. In thrombocytopenic animals lodgement was reduced to 53% (5-HT levels reduced to 50%) of tumor-cell-injected controls. Ketanserin treatment reduced tumor cell lodgement to 72% (5-HT levels to 63%). The results indicate that 5-HT is one of the substances released from activated platelets and that 5-HT is involved in tumor cell lodgement.