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

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.