ArticleBritish journal of cancer2013
Surface proteomic analysis of osteosarcoma identifies EPHA2 as receptor for targeted drug delivery.
Article in British journal of cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed.
- CAR-T cell therapy for pediatric solid tumors: armored CAR-T cells and beyond.Cancer metastasis reviews · 2026Review
- Biological Activity of Biomarkers Associated With Metastasis in Osteosarcoma Cell Lines.Cancer medicine · 2025Article
- PEPN1924, A Phase II Study of Trastuzumab Deruxtecan in Patients With Recurrent Human Epidermal Growth Factor Receptor 2+ Osteosarcoma: A Children's Oncology Group Pediatric Early-Phase Clinical Trial Network Study.JCO oncology advances · 2025Article
- Enhancement of anti-sarcoma immunity by NK cells engineered with mRNA for expression of a EphA2-targeted CAR.Clinical and translational medicine · 2025Article
- Advances on immunotherapy for osteosarcoma.Molecular cancer · 2024Review
- Targeting the EphA2 pathway: could it be the way for bone sarcomas?Cell communication and signaling : CCS · 2024Review
- The EphA2 Receptor Regulates Invasiveness and Drug Sensitivity in Canine and Human Osteosarcoma Cells.Cells · 2024Article
- EphA2-specific microvesicles derived from tumor cells facilitate the targeted delivery of chemotherapeutic drugs for osteosarcoma therapy.Journal of nanobiotechnology · 2024Article
- Overall review of curative impact and barriers of CAR-T cells in osteosarcoma.EXCLI journal · 2024Review
- MiR-210 promotes bone formation in ovariectomized rats by regulating osteogenic/adipogenic differentiation of bone marrow mesenchymal stem cells through downregulation of EPHA2.Journal of orthopaedic surgery and research · 2023Article
- Article
- Combination of protein and cell internalization SELEX identifies a potential RNA therapeutic and delivery platform to treat EphA2-expressing tumors.Molecular therapy. Nucleic acids · 2023Article
- Current status and future challenges of CAR-T cell therapy for osteosarcoma.Frontiers in immunology · 2023Review
- Mass Spectrometric-Based Proteomics for Biomarker Discovery in Osteosarcoma: Current Status and Future Direction.International journal of molecular sciences · 2022Review
- Targeted Delivery of Chemotherapeutic Agents for Osteosarcoma Treatment.Frontiers in oncology · 2022Review
- Review
- Review
- Chimeric Antigen Receptor-modified T cells targeting EphA2 for the immunotherapy of paediatric bone tumours.Cancer gene therapy · 2021Article
- GD2 or HER2 targeting T cell engaging bispecific antibodies to treat osteosarcoma.Journal of hematology & oncology · 2020Article
- Article
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundOsteosarcoma (OS) is the most common bone tumour in children and adolescents. Despite aggressive therapy regimens, treatment outcomes are unsatisfactory. Targeted delivery of drugs can provide higher effective doses at the site of the tumour, ultimately improving the efficacy of existing therapy. Identification of suitable receptors for drug targeting is an essential step in the design of targeted therapy for OS.
methodsWe conducted a comparative analysis of the surface proteome of human OS cells and osteoblasts using cell surface biotinylation combined with nano-liquid chromatography - tandem mass spectrometry-based proteomics to identify surface proteins specifically upregulated on OS cells. This approach generated an extensive data set from which we selected a candidate to study for its suitability as receptor for targeted treatment delivery to OS. First, surface expression of the ephrin type-A receptor 2 (EPHA2) receptor was confirmed using FACS analysis. Ephrin type-A receptor 2 expression in human tumour tissue was tested using immunohistochemistry. Receptor targeting and internalisation studies were conducted to assess intracellular uptake of targeted modalities via EPHA2. Finally, tissue micro arrays containing cores of human OS tissue were stained using immunohistochemistry and EPHA2 staining was correlated to clinical outcome measures.
resultsUsing mass spectrometry, a total of 2841 proteins were identified of which 156 were surface proteins significantly upregulated on OS cells compared with human primary osteoblasts. Ephrin type-A receptor 2 was highly upregulated and the most abundant surface protein on OS cells. In addition, EPHA2 was expressed in a vast majority of human OS samples. Ephrin type-A receptor 2 effectively mediates internalisation of targeted adenoviral vectors into OS cells. Patients with EPHA2-positive tumours showed a trend toward inferior overall survival.
conclusionThe results presented here suggest that the EPHA2 receptor can be considered an attractive candidate receptor for targeted delivery of therapeutics to OS.
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