Adhesion of lymphoma cells to fibronectin: Differential use of alpha(4)beta(1) and alpha(5)beta(1) integrins and stimulation by the 9EG7 mAb against the murine beta(1) integrin subunit

Murine ESb and MDAY-D2 lymphoma cells are highly metastatic, in particular to the liver, and are highly invasive in hepatocyte cultures. This may involve adhesion to hepatocyte surface-associated fibronectin (Kemperman et al., 1994, Cell Adh. and Communic. 2:45). Both ESb and MDAY-D2 cells express the fibronectin receptor alpha(4) beta(1), and MDAY-D2 cells in addition also alpha(5) beta(1). Yet, adhesion of ESb cells to fibronectin was low, and MDAY-D2 cells did not adhere at all, but adhesion of both cells was stimulated by phorbol myristate acetate (PMA) and Mn2+. In ESb cells, this adhesion was mediated by alpha(4) beta(1). In MDAY-D2 cells, however, only alpha(5) beta(1) was involved, despite alpha(4) beta(1) levels similar to ESb cells. The alpha(4) beta(1) integrin was functional since it mediated adhesion of MDAY-D2 cells to VCAM-1. An alpha(5) beta(1)-negative variant of MDAY-D2 adhered to fibronectin and this was mediated by alpha(4) beta(1). These results indicate that alpha(4) beta(1) function in these cells is suppressed in the presence of alpha(5) beta(1). Adhesion of ESb cells to hepatocytes was inhibited by anti-alpha(4) antibody, but only by 30%, and fibronectin adhesion was found to have no role in the interaction of MDAY-D2 cells with hepatocytes. This suggests that alpha(4) beta(1) and alpha(5) beta(1) function is not activated during this interaction. The 9EG7 antibody against mouse beta(1) integrin was described to inhibit beta(1) integrins (Lenter et al., 1993, Proc. Natl. Acad. Sci. USA, 90, 9051). In contrast, we observed that 9EG7 stimulated beta(1)-integrin function: Adhesion of ESb and MDAY-D2 cells not only to fibronectin, but also to laminin was induced or enhanced.