Vessel invasion by tumour cells. An ultrastructural study

The present electron microscopic investigation explored the mechanism through which the cells of an experimental fibrosarcoma implanted in the liver of syngeneic mice broke through the continuous (unperforated) endothelium of peri-tumour veins to enter the blood stream, as well as the immediate reaction of blood cells to the tumour breakthrough. It was found that at their point of contact with the endothelial tube of the peri-tumour vein, the tumour cells caused the endothelial basement membrane to disappear and they entered the vein lumen either by inducing an opening of interendothelial junctions, or by causing intensive vacuolation and disintegration of individual endothelial cells--and thus producing gaps for their passage into the lumen. Both mechanisms of entry were sometimes observed in the same tumour. At their point of breakthrough into the vein lumen, many neoplastic cells were immediately covered by a dense platelet aggregate or they were surrounded by numerous polymorph leucocytes (neutrophils more often than eosinophils) that stuck to their surfaces and sometimes caused a focal disappearance of the tumour cell plasma membrane at the site of polymorph-tumour cell contact. Occasionally polymorph lysosomal granules migrated to such contact areas, and the plasma membrane of the contacting polymorph disappeared as well. Finally, some polymorphs apparently plunged into the cytoplasm of vessel-invading tumour cells, while others were seemingly phagocytised by the latter.