Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

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

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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

    Publikation: Bidrag til tidsskriftReviewForskningpeer review

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

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

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.

OriginalsprogEngelsk
Artikelnummer11452
TidsskriftInternational Journal of Molecular Sciences
Vol/bind22
Udgave nummer21
ISSN1661-6596
DOI
StatusUdgivet - 23 okt. 2021

Bibliografisk note

Funding Information:
Funding: This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska‐Curie grant agreement No 801481 (P.Ç.), the Novo Nordisk Foundation grant no NNF19OC0058603 (N.B.), the Danish Cancer Society grant no R231‐A13820 (N.B.) and R231‐A13832 (L.H.E.), The Research Foundation of the Danish Capital Region (Region Hovedstadens Forskningsfond) (N.B.), Simon Fougner Hartmanns family foundation (L.H.E.).

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

ID: 69005779