Lodgement and extravasation of tumour cells in blood-borne metastasis: an electron microscope study

Soon after i.v. injection of ascites hepatoma cells of rat, 3 types of tumour-cell emboli were found in arterioles and capillaries of the lung. The first type had marked aggregation of platelets and deposition of fibrin. Many were seen when tumour cells with high thromboplastic activity (AH 130) were injected, and were often followed by detachment and fragmentation of endothelial cells. The second type had loosely aggregated platelets and the third type had no aggregation of platelets or deposition of fibrin. The latter 2 types were mainly seen when the tumour cells with low thromboplastic activity [AH 130 F(N)] were injected, and they did not accompany severe structural changes of the endothelial cells. Tumour cell-platelet complexes appeared to be induced by tissue thromboplastin released from tumour cells rather than from the endothelial cells. One to 6 h after injection of AH 130, tumour cells were found beneath the endothelial cells detached from the basement membrane in areas with microthrombi. Breaching of the endothelial cells with the processes of tumour cells was also seen then. Intrusion of the processes of tumour cells into the endothelial cells was noted in groups injected with either AH 130 or AH 130 F(N), but not in the junctions of the endothelial cells. Metastatic foci 3 days after the injection of AH 130 were more frequent than in the rats injected with AH 130 F(N). These results indicate that thromboplastic activity of tumour cells might be important in forming microthrombi in the lodgement phase and might be one of the factors facilitating blood-borne metastasis.