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Secretome Survey of Human Plexiform Neurofibroma Derived Schwann Cells Reveals a Secreted form of the RARRES1 Protein
Children’s National Medical Center, 111 Michigan Avenue NW, Washington, DC 20010, USA
These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 11 June 2012; in revised form: 12 July 2012 / Accepted: 19 July 2012 / Published: 24 July 2012
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.
Keywords: plexiform neurofibroma; Schwann cells; secretome; retinoic acid receptor responder protein1
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Chen, H.-L.; Seol, H.; Brown, K.J.; Gordish-Dressman, H.; Hill, A.; Gallo, V.; Packer, R.; Hathout, Y. Secretome Survey of Human Plexiform Neurofibroma Derived Schwann Cells Reveals a Secreted form of the RARRES1 Protein. Int. J. Mol. Sci. 2012, 13, 9380-9399.
Chen H-L, Seol H, Brown KJ, Gordish-Dressman H, Hill A, Gallo V, Packer R, Hathout Y. Secretome Survey of Human Plexiform Neurofibroma Derived Schwann Cells Reveals a Secreted form of the RARRES1 Protein. International Journal of Molecular Sciences. 2012; 13(7):9380-9399.
Chen, Hui-Ling; Seol, Haeri; Brown, Kristy Jean; Gordish-Dressman, Heather; Hill, Ashley; Gallo, Vittorio; Packer, Roger; Hathout, Yetrib. 2012. "Secretome Survey of Human Plexiform Neurofibroma Derived Schwann Cells Reveals a Secreted form of the RARRES1 Protein." Int. J. Mol. Sci. 13, no. 7: 9380-9399.