Exploring the surfaceome of Ewing sarcoma identifies a new and unique therapeutic target
The cell surface proteome of tumors mediates the interface between the transformed cells and the general microenvironment, including interactions with stromal cells in the tumor niche and immune cells such as T cells. In addition, the cell surface proteome of individual cancers defines biomarkers fo...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
National Academy of Sciences
2016
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| _version_ | 1797056769794506752 |
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| author | Town, J Pais, H Harrison, S Stead, L Bataille, C Bunjobpol, W Zhang, J Rabbitts, T |
| author_facet | Town, J Pais, H Harrison, S Stead, L Bataille, C Bunjobpol, W Zhang, J Rabbitts, T |
| author_sort | Town, J |
| collection | OXFORD |
| description | The cell surface proteome of tumors mediates the interface between the transformed cells and the general microenvironment, including interactions with stromal cells in the tumor niche and immune cells such as T cells. In addition, the cell surface proteome of individual cancers defines biomarkers for thattumor type and potential proteins that can be the target of antibody-mediated therapy. We have used next-generation deep RNA sequencing (RNA-seq) coupled to an inhouse database of genes encoding cell surface proteins (herein referred to as the surfaceome) as a tool to define a cell surface proteome of Ewing sarcoma compared with progenitor mesenchymal stem cells. This subtractive RNA-seq analysis revealed a specific surfaceome of Ewing and showed unexpectedly that the leucine-rich repeat and Ig domain protein 1 (LINGO1) is expressed in over 90% of Ewing sarcoma tumors, but not expressed in any other somatic tissue apart from the brain. We found that the LINGO1 protein acts as a gateway protein internalizing into the tumor cells when engaged by antibody and can carry antibody conjugated with drugs to kill Ewing sarcoma cells. Therefore, LINGO1 is a new, unique, and specific biomarker and drug target for the treatment of Ewing sarcoma. |
| first_indexed | 2024-03-06T19:27:09Z |
| format | Journal article |
| id | oxford-uuid:1c27c829-8850-413f-b090-03346e599efa |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:27:09Z |
| publishDate | 2016 |
| publisher | National Academy of Sciences |
| record_format | dspace |
| spelling | oxford-uuid:1c27c829-8850-413f-b090-03346e599efa2022-03-26T11:04:10ZExploring the surfaceome of Ewing sarcoma identifies a new and unique therapeutic targetJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:1c27c829-8850-413f-b090-03346e599efaEnglishSymplectic Elements at OxfordNational Academy of Sciences2016Town, JPais, HHarrison, SStead, LBataille, CBunjobpol, WZhang, JRabbitts, TThe cell surface proteome of tumors mediates the interface between the transformed cells and the general microenvironment, including interactions with stromal cells in the tumor niche and immune cells such as T cells. In addition, the cell surface proteome of individual cancers defines biomarkers for thattumor type and potential proteins that can be the target of antibody-mediated therapy. We have used next-generation deep RNA sequencing (RNA-seq) coupled to an inhouse database of genes encoding cell surface proteins (herein referred to as the surfaceome) as a tool to define a cell surface proteome of Ewing sarcoma compared with progenitor mesenchymal stem cells. This subtractive RNA-seq analysis revealed a specific surfaceome of Ewing and showed unexpectedly that the leucine-rich repeat and Ig domain protein 1 (LINGO1) is expressed in over 90% of Ewing sarcoma tumors, but not expressed in any other somatic tissue apart from the brain. We found that the LINGO1 protein acts as a gateway protein internalizing into the tumor cells when engaged by antibody and can carry antibody conjugated with drugs to kill Ewing sarcoma cells. Therefore, LINGO1 is a new, unique, and specific biomarker and drug target for the treatment of Ewing sarcoma. |
| spellingShingle | Town, J Pais, H Harrison, S Stead, L Bataille, C Bunjobpol, W Zhang, J Rabbitts, T Exploring the surfaceome of Ewing sarcoma identifies a new and unique therapeutic target |
| title | Exploring the surfaceome of Ewing sarcoma identifies a new and unique therapeutic target |
| title_full | Exploring the surfaceome of Ewing sarcoma identifies a new and unique therapeutic target |
| title_fullStr | Exploring the surfaceome of Ewing sarcoma identifies a new and unique therapeutic target |
| title_full_unstemmed | Exploring the surfaceome of Ewing sarcoma identifies a new and unique therapeutic target |
| title_short | Exploring the surfaceome of Ewing sarcoma identifies a new and unique therapeutic target |
| title_sort | exploring the surfaceome of ewing sarcoma identifies a new and unique therapeutic target |
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