Secretome Survey of Human Plexiform Neurofibroma Derived Schwann Cells Reveals a Secreted form of the RARRES1 Protein

Chen, Huiling; Seol, Haeri; Brown, Kristy J.; Gordish‐Dressman, Heather; Hill, D. Ashley; Gallo, Vittorio; Packer, Roger J.; Hathout, Yetrib

doi:10.3390/ijms13079380

Cited by 8 publications

(5 citation statements)

References 43 publications

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“…Recently, RARRES1 was identified as the major secreted product, probably lacking the N-terminal membrane anchor, from human plexiform neurofibroma-derived Schwann cells (but not normal Schwann cells). 61 This provides further evidence for its primary location in the ER.…”

Section: Discussionmentioning

confidence: 60%

Retinoic acid represses invasion and stem cell phenotype by induction of the metastasis suppressors RARRES1 and LXN

et al. 2013

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The mouse haematopoietic stem cell (SC) regulator Latexin (LXN) is the only known homologue of the retinoic acid receptor responder 1 (RARRES1) gene. Both genes lie adjacent on chromosome 3 and differ mostly by the presence of a transmembrane domain in RARRES1. Despite their homology, it is not known whether they possess similar regulatory mechanisms, cellular localization and function. Here, we identified RARRES1 and LXN as highly significantly downregulated genes in human prostate SCs, whose expression was induced by the pro-differentiation agent all-trans retinoic acid (atRA). AtRA induced expression in the most differentiated cells compared with the SC fraction, suggesting that this subpopulation was less responsive to atRA. Small interfering RNA suppression of RARRES1 and LXN enhanced the SC properties of primary prostate cultures, as shown by a significant increase in their colony-forming ability. Expression of both RARRES1 and LXN was co-ordinately repressed by DNA methylation in prostate cancer cell lines and inhibition of RARRES1 and LXN increased the invasive capacity of primary prostate cultures, which also fully rescued an inhibitory effect induced by atRA. Moreover, we showed that RARRES1 and LXN reside within different sub-cellular compartments, providing evidence that RARRES1 is not a plasma membrane protein as previously supposed but is located primarily in the endoplasmic reticulum; whereas LXN was detected in the nucleus of prostate epithelial cells. Thus, LXN and RARRES1 are potential tumour suppressor genes, which are co-ordinately regulated, SC-silenced genes functioning to suppress invasion and colony-forming ability of prostate cancer cells; yet the proteins reside within different sub-cellular compartments.

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Section: Discussionmentioning

confidence: 60%

Retinoic acid represses invasion and stem cell phenotype by induction of the metastasis suppressors RARRES1 and LXN

et al. 2013

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“…Depending on the cell type, sample preparation, and analysis method the number of proteins identified in the secretome can be different. To the best of our knowledge, mass spectrometry of the Schwann cell secretomes was solely performed in 2 other studies (15, 55). However, these investigations neither addressed differences between differentiation stages nor included the description of secreted proteins derived from repair‐mediating Schwann cells.…”

Section: Discussionmentioning

confidence: 99%

Secretome analysis of nerve repair mediating Schwann cells reveals Smad‐dependent trophism

et al. 2018

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Schwann cells promote nerve regeneration by adaptation of a regenerative phenotype referred to as repair mediating Schwann cell. Down‐regulation of myelin proteins, myelin clearance, formation of Bungner's bands, and secretion of trophic factors characterize this cell type. We have previously shown that the sphingosine‐1‐phosphate receptor agonist Fingolimod/FTY720P promotes the generation of this particular Schwann cell phenotype by activation of dedifferentiation markers and concomitant release of trophic factors resulting in enhanced neurite growth of dorsal root ganglion neurons. Despite its biomedical relevance, a detailed characterization of the corresponding Schwann cell secretóme is lacking, and the impact of FTY720P on enhancing neurite growth is not defined. Here, we applied a label‐free quantitative mass spectrometry approach to characterize the secretomes derived from primary neonatal and adult rat Schwann cells in response to FTY720P. We identified a large proportion of secreted proteins with a high overlap between the neonatal and adult Schwann cells, which can be associated with biologic processes such as development, axon growth, and regeneration. Moreover, FTY720P‐treated Schwann cells release proteins downstream of Smad signaling known to support neurite growth. Our results therefore uncover a network of trophic factors involved in glial‐mediated repair of the peripheral nervous system.—Schira, J., Heinen, A., Poschmann, G., Ziegler, B., Hartung, H.‐P., Stühler, K., Küry, P. Secretome analysis of nerve repair mediating Schwann cells reveals Smad‐dependent trophism. FASEB J. 33, 4703–4715 (2019). http://www.fasebj.org

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“…These primary cell cultures were obtained from healthy donors and included astrocytes, fibroblasts, bronchial epithelial cells, nasal epithelial cells, RPE cells and Schwann cells. These cells were chosen because they were currently studied in our laboratory in the context of different diseases such as brain tumors (astrocytes and GBM cell lines) [11], asthma (bronchial and nasal epithelial cells) [21], age related macular degeneration (RPE cells) [7], and neurofibromatosis type-1 (Schwann cells) [22]. Fibroblasts cells were included as a reference to the primary cell cultures because often primary cell cultures contain fibroblasts cells that might confound the true secretome.…”

Section: Discussionmentioning

confidence: 99%

The human secretome atlas initiative: Implications in health and disease conditions

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Seol

Pillai

et al. 2013

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

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Proteomic analysis of human body fluids is highly challenging, therefore many researchers are redirecting efforts towards secretome profiling. The goal is to define potential biomarkers and therapeutic targets in the secretome that can be traced back in accessible human body fluids. However, currently there is a lack of secretome profiles of normal human primary cells making it difficult to assess the biological meaning of current findings. In this study we sought to establish secretome profiles of human primary cells obtained from healthy donors with the goal of building a human secretome atlas. Such an atlas can be used as a reference for discovery of potential disease associated biomarkers and eventually novel therapeutic targets. As a preliminary study, secretome profiles were established for six different types of human primary cell cultures and checked for overlaps with the three major human body fluids including plasma, cerebrospinal fluid and urine. About 67% of the 1054 identified proteins in the secretome of these primary cells occurred in at least one body fluid. Furthermore, comparison of the secretome profiles of two human glioblastoma cell lines to this new human secretome atlas enabled unambiguous identification of potential brain tumor biomarkers. These biomarkers can be easily monitored in different body fluids using stable isotope labeled standard proteins. The long term goal of this study is to establish a comprehensive online human secretome atlas for future use as a reference for any disease related secretome study.

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Secretome Survey of Human Plexiform Neurofibroma Derived Schwann Cells Reveals a Secreted form of the RARRES1 Protein

Cited by 8 publications

References 43 publications

Retinoic acid represses invasion and stem cell phenotype by induction of the metastasis suppressors RARRES1 and LXN

Retinoic acid represses invasion and stem cell phenotype by induction of the metastasis suppressors RARRES1 and LXN

Secretome analysis of nerve repair mediating Schwann cells reveals Smad‐dependent trophism

The human secretome atlas initiative: Implications in health and disease conditions

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