Exfoliation of plasma membrane components is a directed process that consumes energy and requires active cell metabolism. Proteins involved in regulating the survival and proliferation of eukaryotic cells are released on exfoliated vesicles. We examine here whether the Fas receptor and its cognate ligand ( @entity12 ) are present on vesicles shed from high metastatic potential @entity1 cells and low metastatic potential MIP-101 cells and from HuT 78 cells, respectively. Rates of exfoliation at 2 hours and cumulative levels of extracellular vesicles in serum-free medium conditioned by @entity1 cells are increased by 1.8-fold and 1.6-fold, respectively, relative to that in medium conditioned by MIP-101 cells. Although vesicles shed from both @entity5 cell lines contain @entity1197 , the amount of Fas per vesicle and the percentage of vesicles containing Fas are increased for vesicles isolated from MIP-101 cells, relative to those from @entity1 cells, as determined by immunogold particle labeling and electron microscopy and by immunofluorescence microscopy and flow cytometry. Results of metabolic labeling with 35S- @entity1853 indicate that Fas biosynthesis is reduced by up to 3.3-fold for @entity1 cells, relative to that of MIP-101 cells, consistent with the finding of decreased Fas on vesicles shed from the plasma membrane of @entity1 cells. Although mRNA for soluble Fas receptor is detectable in both cell lines, depletion of shed vesicles from serum-free medium by ultracentrifugation removes all detectable biological activity. @entity12 is detected on vesicles exfoliated from HuT 78 cells by immunoelectron microscopy and Western blot analysis. @entity12 -bearing vesicles induce apoptosis of Fas-expressing @entity5 cells at the same level as observed by treatment with monoclonal anti-Fas antibody. Furthermore, Fas-bearing extracellular vesicles from MIP-101 but not from @entity1 cells protect the @entity1 cell line from @entity12 -induced and anti-Fas-mediated apoptosis, indicating that Fas present on shed vesicles is biologically active. We conclude that the @entity1197 and its cognate ligand are exfoliated from the cell surface in a bioactive configuration. Exfoliation may provide a mechanism for long-range signal-directed apoptosis while maintaining Fas/ @entity12 on a membrane surface.

Biologically active XXXX and its cognate ligand are expressed on plasma membrane-derived extracellular vesicles.

@entity1 :: ('9606', 'Species') :: ['CX-1'] @entity5 :: ('MESH:D009369', 'Disease') :: ['cancer'] @entity1197 :: ('355', 'Gene') :: ['Fas antigen'] @entity1853 :: ('MESH:D008715', 'Chemical') :: ['methionine'] @entity12 :: ('356', 'Gene') :: ['FasL']
@entity1197 :: (355,Gene) :: ['Fas antigen']
