Journal Article

DKFZ-2023-00264

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Dynamics of CXCR4 positive circulating tumor cells in prostate cancer patients during radiotherapy.

Klusa, D. ; Lohaus, F.DKFZ* ; Franken, A. ; Baumbach, M. ; Cojoc, M. ; Dowling, P. ; Linge, A.DKFZ* ; Offermann, A. ; Löck, S. ; Hušman, D. ; Rivandi, M. ; Polzer, B. ; Freytag, V. ; Lange, T. ; Neubauer, H. ; Kücken, M. ; Perner, S. ; Hölscher, T.DKFZ* ; Dubrovska, A. ; Krause, M.DKFZ* ; Kurth, I.DKFZ* ; Baumann, M.DKFZ* ; Peitzsch, C.

2023
Wiley-Liss Bognor Regis

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Please use a persistent id in citations: doi:10.1002/ijc.34457

Abstract: Ablative radiotherapy is a highly efficient treatment modality for patients with metastatic prostate cancer (PCa). However, a subset of patients does not respond. Currently, this subgroup with bad prognosis cannot be identified before disease progression. We hypothesize that markers indicative of radioresistance, stemness, and/or bone tropism may have a prognostic potential to identify patients profiting from the metastases-directed radiotherapy. Therefore, circulating tumor cells (CTCs) were analyzed in patients with metastatic PCa (n=24) during radiotherapy with CellSearch, multi-color flow cytometry and imaging cytometry. Analysis of copy-number alteration indicate a polyclonal CTC population that changes after radiotherapy. CTCs were found in 8 out of 24 patients (33.3 %) and were associated with a shorter time to biochemical progression after radiotherapy. Whereas the total CTC count dropped after radiotherapy, a chemokine receptor CXCR4-expressing subpopulation representing 28.6 % of the total CTC population remained stable up to three months. At once, we observed higher chemokine CCL2 plasma concentrations and pro-inflammatory monocytes. Additional functional analyses demonstrated key roles of CXCR4 and CCL2 for cellular radiosensitivity, tumorigenicity and stem-like potential in vitro and in vivo. Moreover, a high CXCR4 and CCL2 expression was found in bone metastasis biopsies of PCa patients. In summary, panCK+ CXCR4+ CTCs may have a prognostic potential in patients with metastatic PCa treated with metastasis-directed radiotherapy. This article is protected by copyright. All rights reserved.

Keyword(s): CXCR4 ; bone metastasis ; circulating tumor cells ; prostate cancer ; radiotherapy

Note: 2023 Jun 15;152(12):2639-2654

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Contributing Institute(s):

1. DKTK DD zentral (DD01)
2. E220 Radioonkologie Radiobiologie (E220)

Research Program(s):

1. 315 - Bildgebung und Radioonkologie (POF4-315) (POF4-315)

Appears in the scientific report 2023

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Wiley ; Essential Science Indicators ; IF >= 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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