National Center for Tumor Diseases (NCT), Partner Site Dresden, German Cancer Research Center (DKFZ), Heidelberg, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, and Helmholtz-Zentrum Dresden - Rossendorf, Dresden, Germany.
OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden and Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany.
Int J Cancer. 2023 Jun 15;152(12):2639-2654. doi: 10.1002/ijc.34457. Epub 2023 Mar 13.
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.
消融性放射疗法是转移性前列腺癌（PCa）患者的一种高效治疗方式。然而，有一部分患者对此没有反应。目前，无法在疾病进展前识别出这种预后不良的亚组患者。我们假设具有放射抗性、干性和/或骨趋向性的标志物可能具有预测潜力，以识别从转移性放疗中获益的患者。因此，我们在转移性 PCa 患者（n=24）接受放射治疗期间使用 CellSearch、多色流式细胞术和成像细胞术分析了循环肿瘤细胞（CTCs）。拷贝数改变的分析表明 CTC 群体是具有放射抗性的多克隆群体，在放射治疗后发生变化。在 24 名患者中的 8 名（33.3%）中发现了 CTCs，并且与放射治疗后生化进展的时间更短相关。虽然放射治疗后总 CTC 计数下降，但表达趋化因子受体 CXCR4 的亚群占总 CTC 群体的 28.6%，在 3 个月内保持稳定。同时，我们观察到更高的趋化因子 CCL2 血浆浓度和促炎性单核细胞。额外的功能分析表明，CXCR4 和 CCL2 在体外和体内对细胞放射敏感性、肿瘤发生和干性潜能具有关键作用。此外，在 PCa 患者的骨转移活检中发现了高表达的 CXCR4 和 CCL2。综上所述，panCK CXCR4 CTCs 可能具有转移性 PCa 患者接受转移性放疗的预后潜力。
