Factors Within the Endoneurial Microenvironment Act to Suppress Tumorigenesis of MPNST
Background: Deciphering avenues to adequately control malignancies in the peripheral nerve will reduce the need for current, largely-ineffective, standards of care which includes the use of invasive, nerve-damaging, resection surgery. By avoiding the need for en bloc resection surgery, the likelihoo...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2018-10-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fncel.2018.00356/full |
| _version_ | 1818482026015096832 |
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| author | Jo Anne Stratton Jo Anne Stratton Jo Anne Stratton Peggy Assinck Peggy Assinck Sarthak Sinha Ranjan Kumar Aaron Moulson Natalya Patrick Eko Raharjo Jennifer A. Chan Jennifer A. Chan Rajiv Midha Wolfram Tetzlaff Jeff Biernaskie Jeff Biernaskie Jeff Biernaskie |
| author_facet | Jo Anne Stratton Jo Anne Stratton Jo Anne Stratton Peggy Assinck Peggy Assinck Sarthak Sinha Ranjan Kumar Aaron Moulson Natalya Patrick Eko Raharjo Jennifer A. Chan Jennifer A. Chan Rajiv Midha Wolfram Tetzlaff Jeff Biernaskie Jeff Biernaskie Jeff Biernaskie |
| author_sort | Jo Anne Stratton |
| collection | DOAJ |
| description | Background: Deciphering avenues to adequately control malignancies in the peripheral nerve will reduce the need for current, largely-ineffective, standards of care which includes the use of invasive, nerve-damaging, resection surgery. By avoiding the need for en bloc resection surgery, the likelihood of retained function or efficient nerve regeneration following the control of tumor growth is greater, which has several implications for long-term health and well-being of cancer survivors. Nerve tumors can arise as malignant peripheral nerve sheath tumors (MPNST) that result in a highly-aggressive form of soft tissue sarcoma. Although the precise cause of MPNST remains unknown, studies suggest that dysregulation of Schwann cells, mediated by the microenvironment, plays a key role in tumor progression. This study aimed to further characterize the role of local microenvironment on tumor progression, with an emphasis on identifying factors within tumor suppressive environments that have potential for therapeutic application.Methods: We created GFP-tagged adult induced tumorigenic Schwann cell lines (iSCs) and transplanted them into various in vivo microenvironments. We used immunohistochemistry to document the response of iSCs and performed proteomics analysis to identify local factors that might modulate divergent iSC behaviors.Results: Following transplant into the skin, spinal cord or epineurial compartment of the nerve, iSCs formed tumors closely resembling MPNST. In contrast, transplantation into the endoneurial compartment of the nerve significantly suppressed iSC proliferation. Proteomics analysis revealed a battery of factors enriched within the endoneurial compartment, of which one growth factor of interest, ciliary neurotrophic factor (CNTF) was capable of preventing iSCs proliferation in vitro.Conclusions: This dataset describes a novel approach for identifying biologically relevant therapeutic targets, such as CNTF, and highlights the complex relationship that tumor cells have with their local microenvironment. This study has significant implications for the development of future therapeutic strategies to fight MPNSTs, and, consequently, improve peripheral nerve regeneration and nerve function. |
| first_indexed | 2024-12-10T11:42:49Z |
| format | Article |
| id | doaj.art-60c3617d38e24d48ad3780db72698b9d |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-10T11:42:49Z |
| publishDate | 2018-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-60c3617d38e24d48ad3780db72698b9d2022-12-22T01:50:11ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022018-10-011210.3389/fncel.2018.00356413159Factors Within the Endoneurial Microenvironment Act to Suppress Tumorigenesis of MPNSTJo Anne Stratton0Jo Anne Stratton1Jo Anne Stratton2Peggy Assinck3Peggy Assinck4Sarthak Sinha5Ranjan Kumar6Aaron Moulson7Natalya Patrick8Eko Raharjo9Jennifer A. Chan10Jennifer A. Chan11Rajiv Midha12Wolfram Tetzlaff13Jeff Biernaskie14Jeff Biernaskie15Jeff Biernaskie16Hotchkiss Brain Institute, University of Calgary, Calgary, AB, CanadaDepartment of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, CanadaAlberta Children’s Hospital Research Institute, University of Calgary, Calgary, AB, CanadaDepartment of International Collaboration on Repair Discoveries, The University of British Columbia, Vancouver, BC, CanadaGraduate Program in Neuroscience, The University of British Columbia, Vancouver, BC, CanadaDepartment of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, CanadaDepartment of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, CanadaDepartment of International Collaboration on Repair Discoveries, The University of British Columbia, Vancouver, BC, CanadaDepartment of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, CanadaDepartment of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, CanadaArnie Charbonneau Cancer Institute, University of Calgary, Calgary, AB, CanadaDepartment of Pathology and Laboratory Medicine, University of Calgary, Calgary, AB, CanadaDepartment of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB, CanadaDepartment of International Collaboration on Repair Discoveries, The University of British Columbia, Vancouver, BC, CanadaHotchkiss Brain Institute, University of Calgary, Calgary, AB, CanadaDepartment of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, CanadaAlberta Children’s Hospital Research Institute, University of Calgary, Calgary, AB, CanadaBackground: Deciphering avenues to adequately control malignancies in the peripheral nerve will reduce the need for current, largely-ineffective, standards of care which includes the use of invasive, nerve-damaging, resection surgery. By avoiding the need for en bloc resection surgery, the likelihood of retained function or efficient nerve regeneration following the control of tumor growth is greater, which has several implications for long-term health and well-being of cancer survivors. Nerve tumors can arise as malignant peripheral nerve sheath tumors (MPNST) that result in a highly-aggressive form of soft tissue sarcoma. Although the precise cause of MPNST remains unknown, studies suggest that dysregulation of Schwann cells, mediated by the microenvironment, plays a key role in tumor progression. This study aimed to further characterize the role of local microenvironment on tumor progression, with an emphasis on identifying factors within tumor suppressive environments that have potential for therapeutic application.Methods: We created GFP-tagged adult induced tumorigenic Schwann cell lines (iSCs) and transplanted them into various in vivo microenvironments. We used immunohistochemistry to document the response of iSCs and performed proteomics analysis to identify local factors that might modulate divergent iSC behaviors.Results: Following transplant into the skin, spinal cord or epineurial compartment of the nerve, iSCs formed tumors closely resembling MPNST. In contrast, transplantation into the endoneurial compartment of the nerve significantly suppressed iSC proliferation. Proteomics analysis revealed a battery of factors enriched within the endoneurial compartment, of which one growth factor of interest, ciliary neurotrophic factor (CNTF) was capable of preventing iSCs proliferation in vitro.Conclusions: This dataset describes a novel approach for identifying biologically relevant therapeutic targets, such as CNTF, and highlights the complex relationship that tumor cells have with their local microenvironment. This study has significant implications for the development of future therapeutic strategies to fight MPNSTs, and, consequently, improve peripheral nerve regeneration and nerve function.https://www.frontiersin.org/article/10.3389/fncel.2018.00356/fullperipheral nervesarcomaSchwann cellMPNSTCNTFendoneurium |
| spellingShingle | Jo Anne Stratton Jo Anne Stratton Jo Anne Stratton Peggy Assinck Peggy Assinck Sarthak Sinha Ranjan Kumar Aaron Moulson Natalya Patrick Eko Raharjo Jennifer A. Chan Jennifer A. Chan Rajiv Midha Wolfram Tetzlaff Jeff Biernaskie Jeff Biernaskie Jeff Biernaskie Factors Within the Endoneurial Microenvironment Act to Suppress Tumorigenesis of MPNST Frontiers in Cellular Neuroscience peripheral nerve sarcoma Schwann cell MPNST CNTF endoneurium |
| title | Factors Within the Endoneurial Microenvironment Act to Suppress Tumorigenesis of MPNST |
| title_full | Factors Within the Endoneurial Microenvironment Act to Suppress Tumorigenesis of MPNST |
| title_fullStr | Factors Within the Endoneurial Microenvironment Act to Suppress Tumorigenesis of MPNST |
| title_full_unstemmed | Factors Within the Endoneurial Microenvironment Act to Suppress Tumorigenesis of MPNST |
| title_short | Factors Within the Endoneurial Microenvironment Act to Suppress Tumorigenesis of MPNST |
| title_sort | factors within the endoneurial microenvironment act to suppress tumorigenesis of mpnst |
| topic | peripheral nerve sarcoma Schwann cell MPNST CNTF endoneurium |
| url | https://www.frontiersin.org/article/10.3389/fncel.2018.00356/full |
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