Adhesion mechanisms in liver XXXX formation.

@entity706 @entity5 @entity189 @entity1453 @entity3 @entity2071 @entity16445
Our results strongly indicate that integrin mediated adhesion between metastasizing @entity5 cells and hepatocytes has a decisive role in the formation of liver metastases. However, it is also clear that @entity5 cells may use different adhesion pathways and furthermore that the adhesion may be modulated by several factors. The role of adhesion has been demonstrated most clearly for @entity1453 on T cell hybridomas, which interacts with @entity2071 present in the liver. Alternative pathways must exist, however, given the high invasive capacity of ESb cells, which is apparently @entity1453 independent. A possible alternative is adhesion to fibronectin, which is present in abundance on the hepatocyte surface, both in vivo and in vitro. As there is no basement membrane under the endothelium of liver microvessels, so that @entity5 cells cannot adhere to laminin and collagen type IV as in other organs, adhesion to this fibronectin may be particularly important for @entity3 to the liver. Many @entity5 types can use this pathway, and many different fibronectin receptors may be involved, including VLA-4, @entity16445 and several alpha V integrins. For @entity189 there is another possibility: Fibronectin receptor deficient cells may still adhere using the integrin alpha 6 beta 4, which binds to an unknown ligand present on the hepatocyte surface. Modulation of adhesion can occur in several ways. One example is steric hindrance by mucins that may strongly affect and even abrogate adhesion, despite high levels of appropriate integrins. Another is the activation required for integrins on @entity706 cells, the best known example of which is the activation of @entity1453 on T cell hybridomas. It will be evident, therefore, that the role of adhesion in the formation of liver metastases can only be fully understood if the complete set of adhesion molecules on the @entity5 cells is known as well as their functional status and the possible effects of both cellular and extracellular modulating factors.
