1. Dynamics of CXCR4 positive circulating tumor cells in prostate cancer patients during radiotherapy
- Author
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Klusa, D., Lohaus, F., Franken, A., Baumbach, M., Cojoc, M., Dowling, P., Linge, A., Offermann, A., Löck, S., Husman, D., Rivandi, M., Polzer, B., Freytag, V., Lange, T., Neubauer, H., Kücken, M., Perner, S., Hölscher, T., (0000-0002-3375-1500) Dubrovska, A., (0000-0003-1776-9556) Krause, M., Kurth, I., Baumann, M., Peitzsch, C., Klusa, D., Lohaus, F., Franken, A., Baumbach, M., Cojoc, M., Dowling, P., Linge, A., Offermann, A., Löck, S., Husman, D., Rivandi, M., Polzer, B., Freytag, V., Lange, T., Neubauer, H., Kücken, M., Perner, S., Hölscher, T., (0000-0002-3375-1500) Dubrovska, A., (0000-0003-1776-9556) Krause, M., Kurth, I., Baumann, M., and Peitzsch, C.
- 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 Cell-Search, 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.
- Published
- 2023