Injury Signals Cooperate with Nf1 Loss to Relieve the Tumor-Suppressive Environment of Adult Peripheral Nerve
Schwann cells are highly plastic cells that dedifferentiate to a progenitor-like state following injury. However, deregulation of this plasticity, may be involved in the formation of neurofibromas, mixed-cell tumors of Schwann cell (SC) origin that arise upon loss of NF1. Here, we show that adult my...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2013-10-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124713004749 |
| _version_ | 1811299198883069952 |
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| author | Sara Ribeiro Ilaria Napoli Ian J. White Simona Parrinello Adrienne M. Flanagan Ueli Suter Luis F. Parada Alison C. Lloyd |
| author_facet | Sara Ribeiro Ilaria Napoli Ian J. White Simona Parrinello Adrienne M. Flanagan Ueli Suter Luis F. Parada Alison C. Lloyd |
| author_sort | Sara Ribeiro |
| collection | DOAJ |
| description | Schwann cells are highly plastic cells that dedifferentiate to a progenitor-like state following injury. However, deregulation of this plasticity, may be involved in the formation of neurofibromas, mixed-cell tumors of Schwann cell (SC) origin that arise upon loss of NF1. Here, we show that adult myelinating SCs (mSCs) are refractory to Nf1 loss. However, in the context of injury, Nf1-deficient cells display opposing behaviors along the wounded nerve; distal to the injury, Nf1−/− mSCs redifferentiate normally, whereas at the wound site Nf1−/− mSCs give rise to neurofibromas in both Nf1+/+ and Nf1+/− backgrounds. Tracing experiments showed that distinct cell types within the tumor derive from Nf1-deficient SCs. This model of neurofibroma formation demonstrates that neurofibromas can originate from adult SCs and that the nerve environment can switch from tumor suppressive to tumor promoting at a site of injury. These findings have implications for both the characterization and treatment of neurofibromas. |
| first_indexed | 2024-04-13T06:32:37Z |
| format | Article |
| id | doaj.art-2bddeaf657e044ad9dcbe1ebb98bb594 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-13T06:32:37Z |
| publishDate | 2013-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-2bddeaf657e044ad9dcbe1ebb98bb5942022-12-22T02:58:04ZengElsevierCell Reports2211-12472013-10-015112613610.1016/j.celrep.2013.08.033Injury Signals Cooperate with Nf1 Loss to Relieve the Tumor-Suppressive Environment of Adult Peripheral NerveSara Ribeiro0Ilaria Napoli1Ian J. White2Simona Parrinello3Adrienne M. Flanagan4Ueli Suter5Luis F. Parada6Alison C. Lloyd7MRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UKMRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UKMRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UKMRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UKUCL Cancer Institute, University College London, Gower Street, London WC1E 6BT, UKDepartment of Biology, Institute of Molecular Health Sciences, ETH, 8093 Zurich, SwitzerlandDepartment of Developmental Biology and Kent Waldrep Foundation Center for Basic Research on Nerve Growth and Regeneration, University of Texas Southwestern Medical Center, Dallas, TX 75390, USAMRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UKSchwann cells are highly plastic cells that dedifferentiate to a progenitor-like state following injury. However, deregulation of this plasticity, may be involved in the formation of neurofibromas, mixed-cell tumors of Schwann cell (SC) origin that arise upon loss of NF1. Here, we show that adult myelinating SCs (mSCs) are refractory to Nf1 loss. However, in the context of injury, Nf1-deficient cells display opposing behaviors along the wounded nerve; distal to the injury, Nf1−/− mSCs redifferentiate normally, whereas at the wound site Nf1−/− mSCs give rise to neurofibromas in both Nf1+/+ and Nf1+/− backgrounds. Tracing experiments showed that distinct cell types within the tumor derive from Nf1-deficient SCs. This model of neurofibroma formation demonstrates that neurofibromas can originate from adult SCs and that the nerve environment can switch from tumor suppressive to tumor promoting at a site of injury. These findings have implications for both the characterization and treatment of neurofibromas.http://www.sciencedirect.com/science/article/pii/S2211124713004749 |
| spellingShingle | Sara Ribeiro Ilaria Napoli Ian J. White Simona Parrinello Adrienne M. Flanagan Ueli Suter Luis F. Parada Alison C. Lloyd Injury Signals Cooperate with Nf1 Loss to Relieve the Tumor-Suppressive Environment of Adult Peripheral Nerve Cell Reports |
| title | Injury Signals Cooperate with Nf1 Loss to Relieve the Tumor-Suppressive Environment of Adult Peripheral Nerve |
| title_full | Injury Signals Cooperate with Nf1 Loss to Relieve the Tumor-Suppressive Environment of Adult Peripheral Nerve |
| title_fullStr | Injury Signals Cooperate with Nf1 Loss to Relieve the Tumor-Suppressive Environment of Adult Peripheral Nerve |
| title_full_unstemmed | Injury Signals Cooperate with Nf1 Loss to Relieve the Tumor-Suppressive Environment of Adult Peripheral Nerve |
| title_short | Injury Signals Cooperate with Nf1 Loss to Relieve the Tumor-Suppressive Environment of Adult Peripheral Nerve |
| title_sort | injury signals cooperate with nf1 loss to relieve the tumor suppressive environment of adult peripheral nerve |
| url | http://www.sciencedirect.com/science/article/pii/S2211124713004749 |
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