Leukemic cell-endothelial cell interactions in leukemic cell dissemination.
In some human and experimental leukemias and lymphomas, the pattern of metastasis can be correlated with the homing sites of the normal progenitor cells. In vitro binding assays and homing experiments with murine lymphoma cell lines suggest that the nonrandom distribution of metastasis could be determined by specificity of cell-endothelium binding. A single subcutaneous inoculum of L2C cells in strain II guinea pigs resulted in a predictable stereotyped pattern of metastasis. Leukemic cell infiltrates were mainly observed around veins at specific locations in each organ: in brain, the most superficial leptomeningeal veins; in liver, veins of the portal triads; in lung, peribronchial veins; in kidney, veins of the renal columns; in adrenal gland, capsular veins and veins of the medulla. Those vessels also showed intense leukemic cell binding and diapedesis. This would suggest that the leukemic infiltrates were the result of transvenular traffic in these regions. Because leukemic cells were both in the intra- and extravascular compartments, the direction of the cell migration could not be determined. When L2C cells were injected into the right auricle of normal guinea pigs, leukemic cell binding occurred almost exclusively in veins located in areas of metastasis predilection. In addition, extravasation by diapedesis occurred in high endothelial venules in lymphoid organs, peribronchial veins and veins in the portal triads. Neither leukemic cell binding nor diapedesis occurred at the sinusoidal or capillary levels; extravasation in these vessels results from intravascular proliferation and secondary damage of the vessel wall, not by diapedesis. Our data suggest the existence in several organs of the guinea pig of a widely distributed, yet discrete, system of venular endothelial cells specialized in the traffic of leukemic cells.
Azzarelli
B
B
Department of Pathology, Indiana University Medical Center, Indianapolis.
Easterling
K
K
Norton
J A
JA
D000311:Adrenal Glands / Q000098:blood supply / Q000473:pathology; D000818:Animals; D001921:Brain / Q000098:blood supply / Q000473:pathology; D004730:Endothelium, Vascular / Q000473:pathology* / Q000648:ultrastructure; D006168:Guinea Pigs; D007668:Kidney / Q000098:blood supply / Q000473:pathology; D007945:Leukemia, Lymphoid / Q000473:pathology*; D008099:Liver / Q000098:blood supply / Q000473:pathology; D008168:Lung / Q000098:blood supply / Q000473:pathology; D008198:Lymph Nodes / Q000098:blood supply / Q000473:pathology; D008854:Microscopy, Electron; D010581:Peyer's Patches / Q000098:blood supply / Q000473:pathology; D014699:Venules