Involvement of platelet-released 5-HT in tumor cell lodgement

Adherence of circulating tumor cells in the microvasculature (lodgement) is a key event in metastasis formation, once cells released from a primary neoplasm have reached the bloodstream. Platelets appear to be involved in tumor cell lodgement, since thrombocytopenia significantly reduces the number of lodged tumor cells. Platelets activated by tumor cells are known to release 5-HT, and therefore the present study was focused on the influence of this amine on hepatic lodgement of intraportally injected fibrosarcoma cells in rats. Lodgement was quantified by labeling of tumor cells with [5-125I]iodo-2-deoxy-uridine. 5-HT levels were simultaneously determined using liquid chromatography with electrochemical detection (LCED) from hepatic areas with lodged tumor cells, as seen in vital microscopy. Injection of tumor cells increased hepatic 5-HT levels twofold (614 +/- 64 micrograms/g) compared with the levels found in rapidly killed (284 +/- 22 micrograms/g) or saline-injected animals (231 +/- 75 micrograms/g). In thrombocytopenia lodgement was reduced by 47% and hepatic 5-HT levels by 52% in comparison with tumor cell-injected controls. Peripheral blockade of 5-HT2 receptors with ketanserin (0.6 mg/kg sc) also reduced lodgement by 28% and hepatic 5-HT levels by 36%, strongly indicating involvement of platelet-released 5-HT in the lodgement process. Immunocytochemical studies of hepatic tissue in untreated rats demonstrated presence of 5-HT only in mast cells, while as early as 15 min after tumor cell injection 5-HT immunopositive nerves were also seen. This implies an active uptake of circulating 5-HT by neurons.(ABSTRACT TRUNCATED AT 250 WORDS)