The function of multiple extracellular matrix receptors in mediating cell adhesion to extracellular matrix: preparation of monoclonal antibodies to the fibronectin receptor that specifically inhibit cell adhesion to fibronectin and react with platelet glycoproteins Ic-IIa.
We have identified monoclonal antibodies that inhibit human cell adhesion to collagen (P1H5), fibronectin (P1F8 or P1D6), and collagen and fibronectin (P1B5) that react with a family of structurally similar glycoproteins referred to as extracellular matrix receptors (ECMRs) II, VI, and I, respectively. Each member of this family contains a unique alpha subunit, recognized by the antibodies, and a common beta subunit, each of approximately 140 kD. We show here that ECMR VI is identical to the fibronectin receptor (FNR), very late antigen (VLA) 5, and platelet glycoproteins Ic-IIa and shall be referred to as FNR. Monoclonal antibodies to FNR inhibit lymphocyte, fibroblast, and platelet adhesion to fibronectin-coated surfaces. ECMRs I, II, and FNR were differentially expressed in platelets, resting or activated lymphocytes, and myeloid, epithelial, endothelial, and fibroblast cell populations, suggesting a functional role for the receptors in vascular emigration and selective tissue localization. Tissue staining of human fetal skin localized ECMRs I and II to the basal epidermis primarily, while monoclonal antibodies to the FNR stained both the dermis and epidermis. Experiments carried out to investigate the functional roles of these receptors in mediating cell adhesion to complex extracellular matrix (ECM) produced by cells in culture revealed that complete inhibition of cell adhesion to ECM required antibodies to both the FNR and ECMR II, the collagen adhesion receptor. These results show that multiple ECMRs function in combination to mediate cell adhesion to complex EMC templates and predicts that variation in ECM composition and ECMR expression may direct cell localization to specific tissue domains.
Wayner
E A
EA
Department of Biochemical Oncology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.
Carter
W G
WG
Piotrowicz
R S
RS
Kunicki
T J
TJ
D000911:Antibodies, Monoclonal / Q000302:isolation & purification; D000954:Antigens, Surface / Q000378:metabolism; D001665:Binding Sites; D002448:Cell Adhesion; D002460:Cell Line; D003094:Collagen / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005109:Extracellular Matrix / Q000032:analysis / Q000378:metabolism*; D005333:Fetus; D005353:Fibronectins / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D007797:Laminin / Q000378:metabolism; D008954:Models, Biological; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D011233:Precipitin Tests; D011956:Receptors, Cell Surface / Q000032:analysis / Q000502:physiology*; D017469:Receptors, Fibronectin; D011971:Receptors, Immunologic / Q000032:analysis / Q000378:metabolism*; D012867:Skin / Q000032:analysis; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D005353:Fibronectins; D007797:Laminin; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D017469:Receptors, Fibronectin; D011971:Receptors, Immunologic; C052131:extracellular matrix receptor; D003094:Collagen