Multi-cancer detection of circulating tumor cells by targeting oncofetal chondroitin sulfate
Abstract Liquid biopsies for the detection of circulating tumor cells (CTCs) are a promising strategy for personalized cancer management. However, traditional CTC detection platforms are often constrained to epithelial cancers, vulnerable to phenotypic changes, and rely on specialized devices for st...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-05-01
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| Series: | npj Precision Oncology |
| Online Access: | https://doi.org/10.1038/s41698-025-00936-3 |
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| author | Caroline Løppke Randi Ugleholdt Christine F. Secher Nicolai T. Sand Joana Mujollari Tobias Gustavsson Robert Dagil Thor G. Theander Ali Salanti Kristoffer S. Rohrberg Mette Ø. Agerbæk |
| author_facet | Caroline Løppke Randi Ugleholdt Christine F. Secher Nicolai T. Sand Joana Mujollari Tobias Gustavsson Robert Dagil Thor G. Theander Ali Salanti Kristoffer S. Rohrberg Mette Ø. Agerbæk |
| author_sort | Caroline Løppke |
| collection | DOAJ |
| description | Abstract Liquid biopsies for the detection of circulating tumor cells (CTCs) are a promising strategy for personalized cancer management. However, traditional CTC detection platforms are often constrained to epithelial cancers, vulnerable to phenotypic changes, and rely on specialized devices for standardized detection, restricting the clinical utility across diverse cancer types and healthcare settings. In this study, we present a tumor-agnostic, platform-independent CTC detection strategy based on recognition of the cancer-specific glycosylation, oncofetal chondroitin sulfate (ofCS). Through coupling of the ofCS-binding protein, VAR2CSA, to a fluorophore-carrying dextran polymer, we successfully detected ofCS-positive CTCs from blood samples in two diverse and independent cohorts comprising early- and late-stage cancer patients of both epithelial and non-epithelial tumor origin. In addition, no ofCS-positive cells were detected in non-malignant controls. Thus, targeting of ofCS has the potential to expand the range of patients who could benefit from CTC analysis, enhancing the clinical utility in various cancer settings. |
| format | Article |
| id | doaj-art-0f29fd73bbfc490192e8c6086e4b871a |
| institution | DOAJ |
| issn | 2397-768X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Precision Oncology |
| spelling | doaj-art-0f29fd73bbfc490192e8c6086e4b871a2025-08-20T03:10:17ZengNature Portfolionpj Precision Oncology2397-768X2025-05-01911910.1038/s41698-025-00936-3Multi-cancer detection of circulating tumor cells by targeting oncofetal chondroitin sulfateCaroline Løppke0Randi Ugleholdt1Christine F. Secher2Nicolai T. Sand3Joana Mujollari4Tobias Gustavsson5Robert Dagil6Thor G. Theander7Ali Salanti8Kristoffer S. Rohrberg9Mette Ø. Agerbæk10Centre for translational Medicine and Parasitology at Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Disease, Copenhagen University HospitalDepartment of Clinical Medicine, Faculty of Health and Medical Sciences, University of CopenhagenDepartment of Oncology, Copenhagen University HospitalVarCT DiagnosticsCentre for translational Medicine and Parasitology at Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Disease, Copenhagen University HospitalCentre for translational Medicine and Parasitology at Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Disease, Copenhagen University HospitalCentre for translational Medicine and Parasitology at Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Disease, Copenhagen University HospitalCentre for translational Medicine and Parasitology at Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Disease, Copenhagen University HospitalCentre for translational Medicine and Parasitology at Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Disease, Copenhagen University HospitalDepartment of Clinical Medicine, Faculty of Health and Medical Sciences, University of CopenhagenCentre for translational Medicine and Parasitology at Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Disease, Copenhagen University HospitalAbstract Liquid biopsies for the detection of circulating tumor cells (CTCs) are a promising strategy for personalized cancer management. However, traditional CTC detection platforms are often constrained to epithelial cancers, vulnerable to phenotypic changes, and rely on specialized devices for standardized detection, restricting the clinical utility across diverse cancer types and healthcare settings. In this study, we present a tumor-agnostic, platform-independent CTC detection strategy based on recognition of the cancer-specific glycosylation, oncofetal chondroitin sulfate (ofCS). Through coupling of the ofCS-binding protein, VAR2CSA, to a fluorophore-carrying dextran polymer, we successfully detected ofCS-positive CTCs from blood samples in two diverse and independent cohorts comprising early- and late-stage cancer patients of both epithelial and non-epithelial tumor origin. In addition, no ofCS-positive cells were detected in non-malignant controls. Thus, targeting of ofCS has the potential to expand the range of patients who could benefit from CTC analysis, enhancing the clinical utility in various cancer settings.https://doi.org/10.1038/s41698-025-00936-3 |
| spellingShingle | Caroline Løppke Randi Ugleholdt Christine F. Secher Nicolai T. Sand Joana Mujollari Tobias Gustavsson Robert Dagil Thor G. Theander Ali Salanti Kristoffer S. Rohrberg Mette Ø. Agerbæk Multi-cancer detection of circulating tumor cells by targeting oncofetal chondroitin sulfate npj Precision Oncology |
| title | Multi-cancer detection of circulating tumor cells by targeting oncofetal chondroitin sulfate |
| title_full | Multi-cancer detection of circulating tumor cells by targeting oncofetal chondroitin sulfate |
| title_fullStr | Multi-cancer detection of circulating tumor cells by targeting oncofetal chondroitin sulfate |
| title_full_unstemmed | Multi-cancer detection of circulating tumor cells by targeting oncofetal chondroitin sulfate |
| title_short | Multi-cancer detection of circulating tumor cells by targeting oncofetal chondroitin sulfate |
| title_sort | multi cancer detection of circulating tumor cells by targeting oncofetal chondroitin sulfate |
| url | https://doi.org/10.1038/s41698-025-00936-3 |
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