Integrin alpha2beta1 on rat myeloma cells modulates interaction of alpha4beta1 integrin with vascular cell adhesion molecule-1 but not fibronectin.
It is well established that alpha2beta1 integrin functions as a receptor for collagen and laminin; whereas alpha4beta1 integrin binds fibronectin and vascular cell adhesion molecule-1 (VCAM-1). In the present study, we showed that rat myeloma YB2/0 cells constitutively expressed alpha4beta1 but not alpha2beta1 integrin. Transfection of cDNA of mouse a2 integrin subunit resulted in the expression of heterologous alpha2beta1 integrin on YB2/0 cells (YBmalpha2). The expression of alpha2beta1 conferred YBmalpha2 cells the ability to interact with collagen and laminin. In comparison with mock transfected YB2/0 cells (YBpF), YBmalpha2 cells exhibited increases in the binding and migration on VCAM-1; in contrast, both YBpF and YBmalpha2 were similar in their interactions with fibronectin or fibronectin fragment FN-40 that contains the binding site for alpha4beta1 integrin. The interaction of alpha4beta1 with VCAM-1 was further stimulated upon ligation with alpha2beta1-specific mAb. The use of specific inhibitory mAb demonstrated the role of alpha4beta1 in mediating the observed interactions with fibronectin and VCAM-1. Therefore, results show that expression of alpha2beta1 differentially regulated alpha4alpha1 integrin function by stimulating its interactions with VCAM-1 but not fibronectin. The in vivo significance of alpha2beta1 integrin expression was demonstrated by intravital videomicroscopy showing that ligation of alpha2beta1 enhanced alpha4beta1-mediated extravasation of YBmalpha2 cells in the liver.
Chan
Bosco M C
BM
Biotherapeutic Research Group, The John P. Robarts Research Institute, London, Ontario, Canada.
Morris
Vincent L
VL
Hangan-Steinman
Dolores
D
Jarvie
Brenna
B
Cialacu
Mihaela
M
Laansoo
Jaan
J
Hunter
Gregory
G
Wan
Wankei
W
Uniyal
Shashi
S
D000818:Animals; D002465:Cell Movement; D005353:Fibronectins / Q000378:metabolism; D038982:Integrin alpha2beta1 / Q000235:genetics / Q000502:physiology*; D039041:Integrin alpha4beta1 / Q000378:metabolism; D008099:Liver / Q000098:blood supply / Q000166:cytology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D018715:Microscopy, Video; D009101:Multiple Myeloma / Q000473:pathology*; D051381:Rats; D020239:Receptor Cross-Talk / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D005353:Fibronectins; D038982:Integrin alpha2beta1; D039041:Integrin alpha4beta1; D008562:Membrane Glycoproteins; D019010:Vascular Cell Adhesion Molecule-1