Lymphoma cell interaction with cultured vascular endothelial cells and with the subendothelial basal lamina: attachment, invasion and morphological appearance.
Invasion and extravasation of tumor cells through blood vessels and the capillary bed of different organs provide a major pathway for the dissemination and metastatic spread of neoplastic cells. In order to investigate this process in vitro, cloned lines of the low-metastatic methylcholanthrene-induced DBA/2 T lymphoma Eb and its highly metastatic variant line ESb were compared for their mode of interaction (attachment, invasion and morphological appearance) with a confluent monolayer of cultured vascular endothelial cells and with the subendothelial extracellular matrix (ECM). Both the Eb and ESb lymphoma cells exhibited a much faster and firmer attachment to the subendothelium than to the apical surface of the endothelial cell layer. Whereas the Eb cells mostly retained their spheroidal shape when attached to the subendothelium, the ESb cells adopted within 5-24 h a flatter morphology and 30-40% of the cells exhibited an extension of a long pseudopod. Invasion through the endothelial cell layer was faster and occurred to a higher extent with ESb than with Eb cells and was most frequently seen at the edges of an artificial wound made to locally expose the subendothelial basal lamina. Lymphoma cell invasion was most often initiated by a cytoplasmic process indenting at junctions between adjoining endothelial cells and less often traversing through intact cells. Invasion was followed by regeneration of the endothelium and sealing of the invasive cells from the exterior environment. These findings corroborate and extend previous observations on endothelial cell penetration and basement membrane attachment and degradation by various types of metastatic tumor cells. The major new observation comes from the striking contrast in morphological appearance and dynamic behavior between the high- and low-metastatic cells of this tumor system after contact with endothelial cells or their ECM. This suggests a critical role of pseudopod formation and cell motility in endothelial cell penetration and invasion, and thus in an essential step in cancer metastasis.
D000818:Animals; D001485:Basement Membrane / Q000473:pathology; D001808:Blood Vessels / Q000473:pathology*; D002448:Cell Adhesion; D002460:Cell Line; D002478:Cells, Cultured; D004727:Endothelium / Q000473:pathology; D005260:Female; D008223:Lymphoma / Q000473:pathology* / Q000648:ultrastructure; D051379:Mice; D008811:Mice, Inbred DBA; D008855:Microscopy, Electron, Scanning; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000473:pathology / Q000648:ultrastructure