Invasion of Liver Tissue by Tumor Cells and Leukocytes: Comparative Ultrastructure

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Abstract
Experimental invasion of mouse liver tissue by blood-borne lymphosarcoma cells and monocytes, especially the mode of penetration of the sinusoidal endothelium, was studied at the ultrastructural level by serial sections of tissue from (C57BL × DBA)F1 mice. Comparative analysis showed that the behavior of these two types of cells was very similar, with only some quantitative differences. Cells of both types initiated invasion by extending large numbers of thin processes, apparently located randomly over their surfaces. Although many of these processes completely traversed the endothelium, many others merely indented its surface, which indicates that the site of extension of cell processes is not necessarily at preexisting fenestrations. In addition, gaps were found that were not associated with such cell processes. Gaps completely through the endothelium, with or without associated cell processes, were mainly in the thinnest areas of the endothelial cells, but they could be found in thicker parts as well. Serial sections indicated that some gaps were located at junctions between adjoining endothelial cells, but most of them were actually through the endothelial cytoplasm. Migration probably came about by retraction of the endothelial cells, so that the invading cells came gradually into contact with the neighboring hepatocytes. The borders of the endothelial cells still connected by junctions remained intact relatively long during this process. This indicates that the extravasation was essentially transcellular. Meanwhile, the endothelium on the luminal side of the invading cell recovered rapidly. After the migration, the invading cells deeply invaginated the adjacent hepatocytes but without becoming fully intracellular. Small processes from such invaginating cells extended into the hepatocytes surrounding them. Results are discussed in relation to published data on leukocyte diapedesis and invasion and the scanty information available on invasion by tumor cells.