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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Pais, Helio Zhang, Jing Bataille, Carole Bunjobpol, Wilawan Town, Jennifer Stead, Lucy F. Harrison, Sally Rabbitts, Terence H. |
| Description | Author Affiliation: Town J ( Medical Research Council Molecular Haematology Unit, Weatherall Institute for Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, United Kingdom); Pais H ( Medical Research Council Molecular Haematology Unit, Weatherall Institute for Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, United Kingdom); Harrison S ( Leeds Institute of Molecular Medicine, St. James's Hospital, Leeds LS9 7TF, United Kingdom); Stead LF ( Leeds Institute of Molecular Medicine, St. James's Hospital, Leeds LS9 7TF, United Kingdom); Bataille C ( Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Oxford OX1 3AT, United Kingdom.); Bunjobpol W ( Medical Research Council Molecular Haematology Unit, Weatherall Institute for Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, United Kingdom); Zhang J ( Medical Research Council Molecular Haematology Unit, Weatherall Institute for Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, United Kingdom); Rabbitts TH ( Medical Research Council Molecular Haematology Unit, Weatherall Institute for Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, United Kingdom); |
| Abstract | 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 that tumor 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 in-house 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. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 13 |
| Volume Number | 113 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2016-04-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Membrane Proteins Genetics Metabolism Neoplasm Proteins Nerve Tissue Proteins Sarcoma, Ewing Tumor Markers, Biological Immunology Cell Line, Tumor High-Throughput Nucleotide Sequencing Mesenchymal Stromal Cells Proteome RNA, Neoplasm Therapy Sequence Analysis, RNA Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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