The GPIIB-IIIa-like complex may function as a human melanoma cell adhesion receptor for thrombospondin.
The purpose of this study was to determine whether a heterodimeric complex immunologically related to the fibrinogen receptor could function as a thrombospondin (TSP) receptor in TSP-mediated cell-substratum adhesion of human melanoma cells. We found that polyclonal antibodies to the platelet GPIIb-IIIa complex, GPIIIa, and the human vitronectin receptor inhibited TSP-mediated cell adhesion by 63-68%. Immunoprecipitation of detergent extracts of 125I-surface-labeled melanoma cells using either anti-human platelet GPIIb-IIIa or anti-human vitronectin receptor antibody revealed the presence of a single heterodimeric complex, suggesting that both antisera recognize the same integrin receptor, GPIIb-IIIa-like antigen. Adhesion of cells to TSP is likely mediated through a region of the TSP molecule containing the arginine-glycine-aspartic (RGD) peptide sequence, since cell attachment to TSP was inhibited 50-66% in the presence of peptides containing RGD. These results strongly suggest that a GPIIb-IIIa-like/vitronectin receptor can serve as a cell binding site for TSP in mediating cell-substratum adhesion.
Tuszynski
G P
GP
Lankenau Medical Research Center, Philadelphia, Pennsylvania 19151.
Karczewski
J
J
Smith
L
L
Murphy
A
A
Rothman
V L
VL
Knudsen
K A
KA
D000911:Antibodies, Monoclonal; D001792:Blood Platelets / Q000276:immunology*; D018955:CD36 Antigens; D002448:Cell Adhesion; D002460:Cell Line; D006801:Humans; D007106:Immune Sera; D007074:Immunoglobulin G; D008545:Melanoma / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008970:Molecular Weight; D010980:Platelet Membrane Glycoproteins / Q000302:isolation & purification / Q000378:metabolism*; D011975:Receptors, Mitogen / Q000378:metabolism*; D019699:Thrombospondins
D000911:Antibodies, Monoclonal; D018955:CD36 Antigens; D007106:Immune Sera; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D010980:Platelet Membrane Glycoproteins; D011975:Receptors, Mitogen; D019699:Thrombospondins