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.
Driessens
M H
MH
Division of Cell Biology, Netherlands Cancer Institute, Amsterdam.
Van Rijthoven
E A
EA
Kemperman
H
H
Roos
E
E
D000818:Animals; D000911:Antibodies, Monoclonal; D002448:Cell Adhesion / Q000187:drug effects; D005353:Fibronectins / Q000378:metabolism*; D039041:Integrin alpha4beta1; D019012:Integrin beta1 / Q000502:physiology*; D016023:Integrins / Q000032:analysis / Q000502:physiology*; D007797:Laminin / Q000378:metabolism; D008099:Liver / Q000166:cytology; D008223:Lymphoma / Q000737:chemistry / Q000473:pathology*; D051379:Mice; D051381:Rats; D017469:Receptors, Fibronectin / Q000032:analysis / Q000502:physiology*; D016201:Receptors, Lymphocyte Homing / Q000032:analysis / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D005353:Fibronectins; D039041:Integrin alpha4beta1; D019012:Integrin beta1; D016023:Integrins; D007797:Laminin; D017469:Receptors, Fibronectin; D016201:Receptors, Lymphocyte Homing; D013755:Tetradecanoylphorbol Acetate