title: Surface Glycoproteins of Exosomes Shed by Myeloid-Derived Suppressor Cells Contribute to Function.
abstract: In this report, we use a proteomic strategy to identify glycoproteins on the surface of exosomes derived from myeloid-derived suppressor cells (MDSCs), and then test if selected glycoproteins contribute to exosome-mediated chemotaxis and migration of MDSCs. We report successful modification of a surface chemistry method for use with exosomes and identify 21 surface N-glycoproteins on exosomes released by mouse mammary carcinoma-induced MDSCs. These glycoprotein identities and functionalities are compared with 93 N-linked glycoproteins identified on the surface of the parental cells. As with the lysate proteomes examined previously, the exosome surface N-glycoproteins are primarily a subset of the glycoproteins on the surface of the suppressor cells that released them, with related functions and related potential as therapeutic targets. The "don't eat me" molecule CD47 and its binding partners thrombospondin-1 (TSP1) and signal regulatory protein α (SIRPα) were among the surface N-glycoproteins detected. Functional bioassays using antibodies to these three molecules demonstrated that CD47, TSP1, and to a lesser extent SIRPα facilitate exosome-mediated MDSC chemotaxis and migration.
authors.affiliation: Department of Chemistry and Biochemistry, University of Maryland , College Park, Maryland 20742, United States.
authors.forename: Sitara
authors.initials: S
authors.lastname: Chauhan
authors.affiliation: Thermo Fisher Scientific , 355 River Oaks Parkway, San Jose, California 95134, United States.
authors.forename: Steven
authors.initials: S
authors.lastname: Danielson
authors.affiliation: Department of Biological Sciences, University of Maryland Baltimore County , Baltimore, Maryland 21250, United States.
authors.forename: Virginia
authors.initials: V
authors.lastname: Clements
authors.affiliation: Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center , Washington, D.C. 20057, United States.
authors.forename: Nathan
authors.initials: N
authors.lastname: Edwards
authors.affiliation: Department of Biological Sciences, University of Maryland Baltimore County , Baltimore, Maryland 21250, United States.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Ostrand-Rosenberg
authors.affiliation: Department of Chemistry and Biochemistry, University of Maryland , College Park, Maryland 20742, United States.
authors.forename: Catherine
authors.initials: C
authors.lastname: Fenselau
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D051928:CD47 Antigen / Q000235:genetics* / Q000378:metabolism; D002633:Chemotaxis / Q000235:genetics; D055354:Exosomes / Q000737:chemistry / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006031:Glycosylation; D008321:Mammary Glands, Animal; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D000072737:Myeloid-Derived Suppressor Cells / Q000378:metabolism* / Q000473:pathology; D020543:Proteome / Q000235:genetics* / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D019700:Thrombospondin 1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D051928:CD47 Antigen; C497895:Cd47 protein, mouse; D020543:Proteome; C501922:Sirpa protein, mouse; D011971:Receptors, Immunologic; D019700:Thrombospondin 1; C585483:Thbs1 protein, mouse
keywords: N-glycoproteome; cell surface capture; exosomes; myeloid derived suppressor cells