PMN adhesion and extravasation as a paradigm for tumor cell dissemination.
Current evidence indicates that the localization and extravasation of neutrophils is a complex process involving several adhesion molecules with apparently distinct functions, and a highly coordinated and dynamic interplay between the neutrophil and the endothelial cell that is influenced by the shear forces present at the interface between these two cell types. Chemotactic stimulation of the neutrophil not only induces directed locomotion but markedly alters the surface expression and functions of the neutrophil adhesion molecules, having both an upregulating and downregulating influence. Cytokines such as interleukin 1 induce the synthesis and surface expression of endothelial adhesion molecules such as ICAM-1 and ELAM-1, and stimuli such as thrombin and histamine induce the rapid mobilization to the endothelial surface of another adhesion molecule, GMP-140. Transendothelial migration of neutrophils in most settings both in vitro and in vivo appears to require CD18 integrins on the neutrophil and ICAM-1 on the endothelial cells. This is most clearly demonstrated by the genetic deficiency of CD18 in humans, dogs and cattle, where neutrophil extravasation at most inflammatory sites is almost completely absent. Though the coordinated functions of the various neutrophil and endothelial adhesion molecules are highly efficient in promoting neutrophil extravasation, there has been relatively little investigation of their utilization in tumor cell dissemination. Recent results indicate that such studies may prove fruitful. For example, some adenocarcinoma cell lines express the complex carbohydrate (sialyl Lewis x) recently shown to be a ligand for ELAM-1.
Speros P. Martel Leukocyte Biology Laboratory, Department of Pediatrics, Baylor College of Medicine, Houston, TX.
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Smith
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Anderson
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000503:physiopathology; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D009504:Neutrophils / Q000502:physiology*
D015815:Cell Adhesion Molecules