Abstract
The surfaceome is critical because surface proteins provide a gateway for internal signals and transfer of molecules into cells, and surfaceome differences can influence therapy response. We have used a surfaceome analysis method, based on comparing RNA-seq data between normal and abnormal cells (Surfaceome DataBase Mining or Surfaceome DBM), to identify sets of upregulated cell surface protein mRNAs in an LMO2-mediated T-ALL mouse model and corroborated by protein detection using antibodies. In this model the leukemia initiating cells (LICs) comprise pre-leukaemic, differentiation inhibited thymocytes allowing us to provide a profile of the LIC surfaceome in which GPR56, CD53 and CD59a are co-expressed with CD25. Implementation of cell surface interaction assays demonstrates fluid interaction of surface proteins and CD25 is only internalized when co-localized with other proteins. The Surfaceome DBM approach to analyse cancer cell surfaceomes is a way to find targetable surface biomarkers for clinical conditions where RNA-seq data from normal and abnormal cell are available.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / metabolism*
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Animals
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Biomarkers, Tumor / genetics
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Biomarkers, Tumor / metabolism*
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CD59 Antigens / genetics
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CD59 Antigens / metabolism
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Cell Membrane / metabolism
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Cells, Cultured
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HEK293 Cells
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Humans
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Interleukin-2 Receptor alpha Subunit / genetics
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Interleukin-2 Receptor alpha Subunit / metabolism
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LIM Domain Proteins / genetics
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LIM Domain Proteins / metabolism*
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Leukemia, Lymphoid / genetics*
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Leukemia, Lymphoid / metabolism
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Leukemia, Lymphoid / pathology
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Mice
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Neoplastic Stem Cells / metabolism
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism*
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RNA-Seq
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Receptors, G-Protein-Coupled / genetics
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Receptors, G-Protein-Coupled / metabolism
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Tetraspanin 25 / genetics
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Tetraspanin 25 / metabolism
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Transcriptome*
Substances
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Adaptor Proteins, Signal Transducing
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Biomarkers, Tumor
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CD59 Antigens
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GPR56 protein, mouse
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Interleukin-2 Receptor alpha Subunit
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LIM Domain Proteins
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LMO2 protein, human
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Proto-Oncogene Proteins
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Receptors, G-Protein-Coupled
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Tetraspanin 25