The role of integrins and integrin activation in liver metastasis.

An overview is presented of our studies on the interaction between blood-borne tumor cells and the tissues where metastases are formed, in particular the liver. Using blocking antibodies and tumor cell mutants, we have identified the adhesion molecules involved, which so far are all integrins. Strikingly, tumor cell lines that are quite similar, and invade in a comparable fashion, use distinct integrins. Lymphomas that invade the liver massively and diffusely use LFA-1 or fibronectin receptors to adhere to hepatocytes. We have obtained evidence that LFA-1 is activated during the interaction by factors that act through G-protein-coupled receptors, and preliminary results suggest that the same may be true for the fibronectin receptors. Whereas TA3/Ha murine mammary carcinoma cells adhere to hepatocytes via alpha 6 beta 4, TA3/St variant cells of the same tumor bind via the fibronectin receptor alpha 5 beta 1. Adhesion of the TA3/Ha cells appears to be impaired by the mucin epiglycanin that is abundantly present on the surface of these cells.