gms | German Medical Science

68. Kongress der Nordrhein-Westfälischen Gesellschaft für Urologie

Nordrhein-Westfälische Gesellschaft für Urologie e. V.

30.03. - 31.03.2023, Essen

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CDCP1 expression is increased in aggressive urothelial carcinoma and is involved in tumor associated macrophages (TAM) recruitment

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  • presenting/speaker Miriam Saponaro - Department of Urology and Pediatric Urology, University Hospital Bonn, Bonn, Germany; Center for Integrated Oncology Cologne/Bonn, University Hospital Bonn, Bonn, Germany
  • Nicolas Mönig - Department of Urology and Pediatric Urology, University Hospital Bonn, Bonn, Germany; Center for Integrated Oncology Cologne/Bonn, University Hospital Bonn, Bonn, Germany
  • Markus Eckstein - University of Erlangen-Nuremberg, Erlangen-Nuremberg, Germany
  • Sebastian Liene - Institute of Experimental Oncology, University Hospital Bonn, Bonn, Germany; Center for Integrated Oncology Cologne/Bonn, University Hospital Bonn, Bonn, Germany
  • Sina Flottmann - Department of Urology and Pediatric Urology, University Hospital Bonn, Bonn, Germany; Center for Integrated Oncology Cologne/Bonn, University Hospital Bonn, Bonn, Germany
  • Maike Effern - Institute of Experimental Oncology, University Hospital Bonn, Bonn, Germany; Center for Integrated Oncology Cologne/Bonn, University Hospital Bonn, Bonn, Germany
  • Anja Winkler - Department of Urology and Pediatric Urology, University Hospital Bonn, Bonn, Germany; Center for Integrated Oncology Cologne/Bonn, University Hospital Bonn, Bonn, Germany
  • Doris Schmidt - Department of Urology and Pediatric Urology, University Hospital Bonn, Bonn, Germany; Center for Integrated Oncology Cologne/Bonn, University Hospital Bonn, Bonn, Germany
  • Karin Wörsdörfer - Department of Urology and Pediatric Urology, University Hospital Bonn, Bonn, Germany; Center for Integrated Oncology Cologne/Bonn, University Hospital Bonn, Bonn, Germany
  • Niklas Klümper - Department of Urology and Pediatric Urology, University Hospital Bonn, Bonn, Germany; Center for Integrated Oncology Cologne/Bonn, University Hospital Bonn, Bonn, Germany
  • Manuel Ritter - Department of Urology and Pediatric Urology, University Hospital Bonn, Bonn, Germany; Center for Integrated Oncology Cologne/Bonn, University Hospital Bonn, Bonn, Germany
  • Michael Hölzel - Institute of Experimental Oncology, University Hospital Bonn, Bonn, Germany; Center for Integrated Oncology Cologne/Bonn, University Hospital Bonn, Bonn, Germany
  • Abdullah Alajati - Department of Urology and Pediatric Urology, University Hospital Bonn, Bonn, Germany; Center for Integrated Oncology Cologne/Bonn, University Hospital Bonn, Bonn, Germany

Nordrhein-Westfälische Gesellschaft für Urologie. 68. Kongress der Nordrhein-Westfälischen Gesellschaft für Urologie. Essen, 30.-31.03.2023. Düsseldorf: German Medical Science GMS Publishing House; 2023. DocP 1.13

doi: 10.3205/23nrwgu48, urn:nbn:de:0183-23nrwgu480

Veröffentlicht: 28. März 2023

© 2023 Saponaro et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.

Gliederung

Text

Introduction: CDCP1 is a transmembrane protein that is frequently overexpressed in a variety of human cancers and its expression correlates with invasion and metastases. However, the role of CDCP1 in urothelial cancer (UC) remains poorly characterized. Thus, the aim of this study is to define how CDCP1 influence tumor progression in the urothelium. Moreover, as tumor microenvironment (TME) is relevant in tumor biology, we aimed to investigate the interplay between tumor associated macrophages (TAM) and tumor cells expressing CDCP1.

Material & Methods: Immunohistochemistry (IHC) analyses were performed in two independent cohorts, counting 331 human UC specimens in total, and CDCP1 expression levels were assessed together with CD163 and CD68. Knockout of CDCP1 (CDCP1-KO) was performed with CRISPR-Cas9 method on UC cell lines (T24 and TCCSUP). Survival, migration and activity of PBMC-derived macrophages were tested upon the stimulation with supernatant collected from CDCP1-KO and wild type (WT) cells.

Results: IHC analyses revealed a strong correlation between CDCP1 levels and a shortened patients’ survival. Moreover, tumors expressing CDCP1 were enriched in CD163 and CD68 positive cells. In-vitro experiments performed on PBMC-derived macrophages showed a reduction in survival, migration and activity after the treatment with supernatant from CDCP1-KO cells.

Conclusion: This study demonstrates that CDCP1 overexpression is correlated to a shorter patients’ lifespan. Considering the observed enrichment in CD68 and CD163 positive populations, the effect on patients survival might be driven by TAM recruitment in the tumor site.