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The collagen receptor uparap in malignant mesothelioma: A potential diagnostic marker and therapeutic target

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  1. Correlation of MET-Receptor Overexpression with MET Gene Amplification and Patient Outcome in Malignant Mesothelioma

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Classification of MSH6 Variants of Uncertain Significance Using Functional Assays

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  1. Long-Term Changes in Invasive Physiological Pressure Indices of Stenosis Severity Following Transcatheter Aortic Valve Implantation

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  2. Correlation of MET-Receptor Overexpression with MET Gene Amplification and Patient Outcome in Malignant Mesothelioma

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  3. Clopidogrel, prasugrel, and ticagrelor for all-comers with ST-segment elevation myocardial infarction

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Malignant mesothelioma (MM) is a highly aggressive cancer with limited therapeutic options. We have previously shown that the endocytic collagen receptor, uPARAP, is upregulated in certain cancers and can be therapeutically targeted. Public RNA expression data display uPARAP overexpression in MM. Thus, to evaluate its potential use in diagnostics and therapy, we quantified uPARAP expression by immunohistochemical H‐score in formalin‐fixed paraffin‐embedded bioptic/surgical human tissue samples and tissue microarrays. We detected pronounced upregulation of uPARAP in the three main MM subtypes compared to non‐malignant reactive mesothelial proliferations, with higher expression in sarcomatoid and biphasic than in epithelioid MM. The upregulation appeared to be independent of patients’ asbestos exposure and unaffected after chemotherapy. Using immunoblotting, we demonstrated high expression of uPARAP in MM cell lines and no expression in a non‐malignant mesothelial cell line. Moreover, we showed the specific internalization of an anti‐uPARAP monoclonal antibody by the MM cell lines using flow cytometry‐based assays and confocal microscopy. Finally, we demonstrated the sensitivity of these cells towards sub‐nanomolar concentrations of an antibody‐drug conjugate formed with the uPARAP‐directed antibody and a potent cytotoxin that led to efficient, uPARAP‐specific eradication of the MM cells. Further studies on patient cohorts and functional preclinical models will fully reveal whether uPARAP could be exploited in diagnostics and therapeutic targeting of MM.

Original languageEnglish
Article number11452
JournalInternational Journal of Molecular Sciences
Volume22
Issue number21
ISSN1661-6596
DOIs
Publication statusPublished - 23 Oct 2021

Bibliographical note

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

    Research areas

  • ADC, Antibody‐drug conjugate, CD280, Endo180, Extracellular matrix, Immunohistochemistry, Mesothelioma, MRC2, Tumor microenvironment, UPARAP

ID: 69005779