MODULATION OF IN-VIVO MIGRATORY FUNCTION OF ALPHA-2-BETA-1 INTEGRIN IN MOUSE-LIVER

We report herein that expression of alpha 2 beta 1 integrin increased human erythroleukemia K562 transfectant (KX2C2) cell movement after ex travasation into liver parenchyma. In contrast a previous study demons trated that alpha 2 beta 1 expression conferred a stationary phenotype to human rhabdomyosarcoma RD transfectant (RDX2C2) cells after extrav asation into the liver. We therefore assessed the adhesive and migrato ry function of alpha 2 beta 1 on KX2C2 and RDX2C2 cells using a alpha 2 beta 1-specific stimulatory monoclonal antibody (mAb), JBS2, and a b locking mAb, BHA2.1. In comparison with RDX2C2 cells, KX2C2 were only weakly adherent to collagen and laminin. JBS2 stimulated alpha 2 beta 1-mediated interaction of KX2C2 cells with both collagen and laminin r esulting in increases in cell movement on both matrix proteins. In the presence of Mn2+, JBS2-stimulated adhesion on collagen beyond an opti mal level for cell movement. In comparison, an increase in RDX2C2 cell movement on collagen required a reduction in its adhesive strength pr ovided by the blocking mAb BHA2.1. Consistent with these in vitro find ings, in vivo videomicroscopy revealed that alpha 2 beta 1-mediated po stextravasation cell movement of KX2C2 cells in the liver tissue could also be stimulated by JBS2. Thus, results demonstrate that alpha 2 be ta 1 expression can modulate postextravasation cell movement by confer ring either a stationary or motile phenotype to different cell types. These findings may be related to the differing metastatic activities o f different tumor cell types.