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

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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 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.

Details

Original languageEnglish
Pages (from-to)2639-2654
Number of pages16
JournalInternational journal of cancer
Volume152
Issue number12
Publication statusPublished - 15 Jun 2023
Peer-reviewedYes

External IDs

PubMed 36733230
Mendeley ef2aa6f5-1421-3e18-be17-1ffe33613969
WOS 000948758800001
ORCID /0000-0002-5247-908X/work/142241953
ORCID /0000-0002-7017-3738/work/142254031

Keywords

Subject groups, research areas, subject areas according to Destatis

Sustainable Development Goals

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Keywords

  • bone metastasis, circulating tumor cells, CXCR4, prostate cancer, radiotherapy, Bone metastasis, Cxcr4, Circulating tumor cells, Radiotherapy, Prostate cancer, Prognosis, Prostatic Neoplasms/radiotherapy, Humans, Male, Neoplastic Cells, Circulating/pathology, Biomarkers, Tumor, Bone Neoplasms/pathology, Receptors, CXCR4

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