title: Peptide-based systems analysis of inflammation induced myeloid-derived suppressor cells reveals diverse signaling pathways.
abstract: A better understanding of molecular signaling between myeloid-derived suppressor cells (MDSC), tumor cells, T-cells, and inflammatory mediators is expected to contribute to more effective cancer immunotherapies. We focus on plasma membrane associated proteins, which are critical in signaling and intercellular communication, and investigate changes in their abundance in MDSC of tumor-bearing mice subject to heightened versus basal inflammatory conditions. Using spectral counting, we observed statistically significant differential abundances for 35 proteins associated with the plasma membrane, most notably the pro-inflammatory proteins S100A8 and S100A9 which induce MDSC and promote their migration. We also tested whether the peptides associated with canonical pathways showed a statistically significant increase or decrease subject to heightened versus basal inflammatory conditions. Collectively, these studies used bottom-up proteomic analysis to identify plasma membrane associated pro-inflammatory molecules and pathways that drive MDSC accumulation, migration, and suppressive potency.
authors.affiliation: Department of Chemistry and Biochemistry, University of Maryland, College Park, MD, USA.|Department of Biochemistry, Faculty of Science, Burapha University, Chonburi, Thailand.
authors.forename: Waeowalee
authors.initials: W
authors.lastname: Choksawangkarn
authors.affiliation: Department of Chemistry and Biochemistry, University of Maryland, College Park, MD, USA.
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Graham
authors.affiliation: Department of Chemistry and Biochemistry, University of Maryland, College Park, MD, USA.
authors.forename: Meghan
authors.initials: M
authors.lastname: Burke
authors.affiliation: Department of Chemistry and Biochemistry, University of Maryland, College Park, MD, USA.|Graduate School of Nanoscience and Technology (WCU), Korea Advanced Institute of Science and Technology, Daejeon, Korea.
authors.forename: Sang Bok
authors.initials: SB
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences, University of Maryland Baltimore County, Baltimore, MD, USA.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Ostrand-Rosenberg
authors.affiliation: Department of Chemistry and Biochemistry, University of Maryland, College Park, MD, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Fenselau
authors.affiliation: Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, DC, USA.
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: Edwards
mesh_terms: D000818:Animals; D040501:Calgranulin A / Q000276:immunology; D040502:Calgranulin B / Q000276:immunology; D002465:Cell Movement; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D007249:Inflammation / Q000150:complications / Q000276:immunology*; D008565:Membrane Proteins / Q000276:immunology*; D008807:Mice, Inbred BALB C; D000072737:Myeloid-Derived Suppressor Cells / Q000276:immunology*; D009369:Neoplasms / Q000150:complications / Q000276:immunology*; D040901:Proteomics; D053719:Tandem Mass Spectrometry
chemical_list: D040501:Calgranulin A; D040502:Calgranulin B; D008565:Membrane Proteins; C576329:S100A9 protein, mouse; C086145:S100a8 protein, mouse
keywords: Cell migration; Differential protein expression; Immune suppression; Inflammation; Mass spectrometry - LC-MS/MS; Myeloid-derived suppressor cells; Systems biology