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

• Published in: International journal of cancer Vol. 152; no. 12; pp. 2639 - 2654
• Main Authors: Klusa, Daria, Lohaus, Fabian, Franken, Andre, Baumbach, Marian, Cojoc, Monica, Dowling, Paul, Linge, Annett, Offermann, Anne, Löck, Steffen, Hušman, Dejan, Rivandi, Mahdi, Polzer, Bernhard, Freytag, Vera, Lange, Tobias, Neubauer, Hans, Kücken, Michael, Perner, Sven, Hölscher, Tobias, Dubrovska, Anna, Krause, Mechthild, Kurth, Ina, Baumann, Michael, Peitzsch, Claudia
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 15.06.2023
• Subjects: Biomarkers, Tumor; Biopsy; Bone Neoplasms - pathology; Cancer; Chemokine receptors; Chemokines; CXCR4 protein; Flow cytometry; Humans; Inflammation; Male; Medical research; Metastases; Metastasis; Monocyte chemoattractant protein 1; Monocytes; Neoplastic Cells, Circulating - pathology; Prognosis; Prostate cancer; Prostatic Neoplasms - pathology; Prostatic Neoplasms - radiotherapy; Radiation therapy; Radioresistance; Radiosensitivity; Receptors, CXCR4; Tropism; Tumor cells; Tumorigenicity; radiotherapy; CXCR4; prostate cancer; bone metastasis; circulating tumor cells
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.34457

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.