Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany.
Department of Biotechnology and Biophysics, Biocenter, Julius-Maximilians-University Würzburg, Würzburg, Germany.
Leuk Lymphoma. 2022 Oct;63(10):2393-2402. doi: 10.1080/10428194.2022.2074986. Epub 2022 Jul 8.
Chemokine receptors represent novel targets for treatment of multiple myeloma (MM). However, CXCR4 expression appears to be highly dynamic. This study investigated the impact of commonly used anti-myeloma agents on CXCR4 expression. Established human myeloma cell lines as well as patient-derived CD138 plasma cells were exposed to antineoplastic drugs. Cells were analyzed for CXCR4 expression by flow cytometry and stochastic optical reconstruction microscopy (STORM). In addition, cellular uptake of Ga-Pentixafor, a PET radiotracer for noninvasive assessment of CXCR4 expression , was assessed. CXCR4 expression was highly variable and turned out to be substance, dose and time dependent. Treatment with bortezomib was associated with reduced expression, while dexamethasone and doxorubicin significantly increased expression of CXCR4. Combination of these compounds further increased CXCR4 expression. In conclusion, drugs or combination of drugs can induce CXCR4 expression in myeloma cells. Hence, pretreatment may impact on response to CXCR4-based therapies.
趋化因子受体是治疗多发性骨髓瘤（MM）的新靶点。然而，CXCR4 的表达似乎具有高度动态性。本研究探讨了常用骨髓瘤治疗药物对 CXCR4 表达的影响。将已建立的人骨髓瘤细胞系和患者来源的 CD138 浆细胞暴露于抗肿瘤药物中。通过流式细胞术和随机光学重建显微镜（STORM）分析细胞中 CXCR4 的表达。此外，还评估了 Ga-Pentixafor 的细胞摄取，Ga-Pentixafor 是一种用于非侵入性评估 CXCR4 表达的 PET 示踪剂。CXCR4 的表达高度可变，且取决于物质、剂量和时间。硼替佐米治疗与表达减少相关，而地塞米松和阿霉素显著增加 CXCR4 的表达。这些化合物的组合进一步增加了 CXCR4 的表达。总之，药物或药物组合可诱导骨髓瘤细胞中 CXCR4 的表达。因此，预处理可能会影响基于 CXCR4 的治疗的反应。
