Involvement of platelets and coagulation systems in the hematogenous metastasis of tumor cells has been suggested from in vivo and in vitro studies, however, there is still controversy about the exact role of hemostasis in metastasis. To date, at least three types of platelet aggregating mechanisms and three types of tumor cell procoagulants have been reported in different tumor cells.We investigated platelet aggregating activity (PAA), procoagulant activity (PCA) and the relationship between these two activities, using eight human neuroblastoma cell lines, three human leukemia cell lines and human mature lymphocytes. PCA in tumor cells was measured by the single stage recalcification time and the assay with chromogenic substrate S2222. PAA was determined turbidometrically with an aggregometer by adding cell suspensions of tumor cells to platelet rich plasma (PRP). The effects of protease inhibitors, enzymes and thrombin inhibitors on PAA and PCA were also studied.Neuroblastoma cell suspensions showed high PCAs which were reduced in Factor VII deficient human plasma, indicating a tissue factor-like activity. NCG line possessing the highest PCA also showed a high PAA, which was inhibited by pretreatment of cell suspensions with phospholipase A2 and abolished in the presence of heparin, hirudin or MD805 in the assay system. Human leukemia cell lines and mature lymphocytes had weak to moderate PCAs without showing PAA, but became active to express PAA after being removed of cell surface sialic acid by neuraminidase. These results suggest that in neuroblastoma, PCA closely linked with PAA may play a role in the hematogenous metastasis. In hemopoietic cells, PAA expressed when cell surface sialic acid is removed does not correlate with PCA, and sialic acid in these cells possibly prevents direct interaction with platelets in the hemostatic homeostasis.
Cofilin determines the migration behavior and turning frequency of metastatic cancer cells
