Tissue factor is the receptor for plasminogen type 1 on 1-LN human prostate cancer cells.
Tissue factor (TF), the initiator of the extrinsic pathway of coagulation, binds plasminogen (Pg) with high affinity through an interaction between kringles 1-3 of Pg and the extracellular domain of TF. We investigated the binding of Pg type 1 (Pg 1) and Pg type 2 (Pg 2) to highly invasive, TF-expressing, 1-LN human prostate tumor cells and to TF isolated from 1-LN cell membranes. Pg 1, containing both N-linked and O-linked oligosaccharide chains, bound to isolated TF with high affinity, whereas Pg 2, containing only one O-linked oligosaccharide chain, did not bind to TF. Although Pg 1 and Pg 2 bind to 1-LN cells, only anti-TF antibodies inhibited the binding of Pg 1, suggesting that TF functions as the receptor for Pg 1 on 1-LN cells. Binding of Pg 1 to isolated TF was inhibited by 6-aminohexanoic acid and alpha-methylmannoside, suggesting that Pg 1 L-lysine binding sites and the biantennary, mannose-containing N-linked oligosaccharide chain are involved in this interaction. Binding of Pg 1 to 1-LN cells promoted activation by receptor-bound urinary-type Pg activator (u-PA) and initiated a Ca(++) signaling cascade. In previous studies we demonstrated that the Pg 2 O-linked carbohydrate chain is essential for its binding to CD26 on 1-LN cells. The current studies suggest that Pg oligosaccharide chains regulate the binding of Pg 1 and Pg 2 to separate receptors on the cell surface.
Gonzalez-Gronow
Mario
M
Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA. gonza002@mc.duke.edu
Gawdi
Govind
G
Pizzo
Salvatore V
SV
D001665:Binding Sites; D020013:Calcium Signaling / Q000187:drug effects; D006031:Glycosylation; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects; D009361:Neoplasm Invasiveness; D009844:Oligosaccharides; D010958:Plasminogen / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D013925:Thromboplastin / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000494:pharmacology
D009844:Oligosaccharides; D010958:Plasminogen; D013925:Thromboplastin; D014568:Urokinase-Type Plasminogen Activator; D020780:Matrix Metalloproteinase 9