Skertich Nicholas J, Chu Fei, Tarhoni Imad A M, Szajek Stephen, Borgia Jeffrey A, Madonna Mary Beth
Department of Surgery, Division of Pediatric Surgery, Rush University Medical Center, Chicago, IL 60612, USA.
Department of Pathology, Rush University Medical Center, Chicago, IL 60612, USA.
Cancers (Basel). 2022 Jan 31;14(3):751. doi: 10.3390/cancers14030751.
Neuroblastoma is a common childhood cancer with poor prognosis when at its advanced stage. Checkpoint molecule inhibition is successful in treating multiple advanced adult cancers. We investigated PD-L1 and other checkpoint molecule expression to determine their roles in drug resistance and usefulness as targets for drug therapy. We developed three doxorubicin-resistant (DoxR) cell lines from parental cell lines. Matrigel in vitro invasion assays were used to compare invasiveness. Western blot assays were used to compare PD-L1 expression. Immuno-oncology checkpoint protein panels were used to compare concentrations of 17 checkpoint molecules both cellular and soluble. PD-L1 and 12 other checkpoint molecules were present in all cell lysates of each cell line without significantly different levels. Three were solubilized in the media of each cell line. PD-L1 is expressed in all DoxR and parental neuroblastoma cells and may be a potential target for drug therapy although its role in drug resistance remains unclear. Benchmarking checkpoint molecules provides the basis for future studies identifying targets for directed therapy and biomarkers for cancer detection or prognosis.
神经母细胞瘤是一种常见的儿童癌症，晚期预后较差。检查点分子抑制在治疗多种晚期成人癌症方面取得了成功。我们研究了程序性死亡受体配体1（PD-L1）和其他检查点分子的表达，以确定它们在耐药性中的作用以及作为药物治疗靶点的有效性。我们从亲代细胞系中开发了三种耐阿霉素（DoxR）细胞系。使用基质胶体外侵袭试验来比较侵袭性。使用蛋白质免疫印迹试验来比较PD-L1的表达。使用免疫肿瘤检查点蛋白检测板来比较17种检查点分子在细胞和可溶性成分中的浓度。PD-L1和其他12种检查点分子存在于每个细胞系的所有细胞裂解物中，水平无显著差异。其中三种在每个细胞系的培养基中可溶。PD-L1在所有耐阿霉素和神经母细胞瘤亲代细胞中均有表达，尽管其在耐药性中的作用尚不清楚，但可能是药物治疗的潜在靶点。对检查点分子进行基准测试为未来研究确定定向治疗靶点以及癌症检测或预后生物标志物提供了基础。
