Dynamics of CXCR4 positive circulating tumor cells in prostate cancer patients during radiotherapy

  • Daria Klusa
  • Fabian Lohaus
  • Andre Franken
  • Marian Baumbach
  • Monica Cojoc
  • Paul Dowling
  • Annett Linge
  • Anne Offermann
  • Steffen Löck
  • Dejan Hušman
  • Mahdi Rivandi
  • Bernhard Polzer
  • Vera Freytag
  • Tobias Lange
  • Hans Neubauer
  • Michael Kücken
  • Sven Perner
  • Tobias Hölscher
  • Anna Dubrovska
  • Mechthild Krause
  • Ina Kurth
  • Michael Baumann
  • Claudia Peitzsch


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 metastases-directed radiotherapy. Therefore, circulating tumor cells (CTCs) were analyzed in patients with metastatic PCa (n = 24) during radiotherapy with CellSearch, multicolor flow cytometry and imaging cytometry. Analysis of copy-number alteration indicates 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 3 months. At once, we observed higher chemokine CCL2 plasma concentrations and proinflammatory 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.

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Original languageEnglish
Publication statusPublished - 15.06.2023

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PubMed 36733230