title: Secretome survey of human plexiform neurofibroma derived Schwann Cells reveals a secreted form of the RARRES1 protein.
abstract: To bring insights into neurofibroma biochemistry, a comprehensive secretome analysis was performed on cultured human primary Schwann cells isolated from surgically resected plexiform neurofibroma and from normal nerve tissue. Using a combination of SDS-PAGE and high precision LC-MS/MS, 907 proteins were confidently identified in the conditioned media of Schwann cell cultures combined. Label free proteome profiling revealed consistent release of high levels of 22 proteins by the four biological replicates of NF1 Schwann cell cultures relative to the two normal Schwann cell cultures. Inversely, 9 proteins displayed decreased levels in the conditioned media of NF1 relative to normal Schwann cells. The proteins with increased levels included proteins involved in cell growth, angiogenesis and complement pathway while proteins with decreased levels included those involved in cell adhesion, plasminogen pathway and extracellular matrix remodeling. Retinoic acid receptor responder protein-1 (RARRES1), previously described as an integral membrane tumor suppressor, was found exclusively secreted by NF1 Schwann cells but not by normal Schwann cells. All-trans retinoic acid modulated secretion of RARRES1 in a dose dependent manner. This study shows altered secretion of key proteins in NF1 derived Schwann cells. The potential implication of these proteins in neurofibroma biology is discussed.
authors.affiliation: Children's National Medical Center, 111 Michigan Avenue NW, Washington, DC 20010, USA.
authors.forename: Hui-Ling
authors.initials: HL
authors.lastname: Chen
authors.affiliation: Children's National Medical Center, 111 Michigan Avenue NW, Washington, DC 20010, USA.
authors.forename: Haeri
authors.initials: H
authors.lastname: Seol
authors.affiliation: Children's National Medical Center, 111 Michigan Avenue NW, Washington, DC 20010, USA.
authors.forename: Kristy Jean
authors.initials: KJ
authors.lastname: Brown
authors.affiliation: Children's National Medical Center, 111 Michigan Avenue NW, Washington, DC 20010, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Gordish-Dressman
authors.affiliation: Children's National Medical Center, 111 Michigan Avenue NW, Washington, DC 20010, USA.
authors.forename: Ashley
authors.initials: A
authors.lastname: Hill
authors.affiliation: Children's National Medical Center, 111 Michigan Avenue NW, Washington, DC 20010, USA.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Gallo
authors.affiliation: Children's National Medical Center, 111 Michigan Avenue NW, Washington, DC 20010, USA.
authors.forename: Roger
authors.initials: R
authors.lastname: Packer
authors.affiliation: Children's National Medical Center, 111 Michigan Avenue NW, Washington, DC 20010, USA.
authors.forename: Yetrib
authors.initials: Y
authors.lastname: Hathout
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D018318:Neurofibroma, Plexiform / Q000378:metabolism* / Q000473:pathology; D012583:Schwann Cells / Q000378:metabolism* / Q000473:pathology; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C452562:RARRES1 protein, human; D014212:Tretinoin