Division of Mechanical and Biomedical Engineering, Ewha Womans University, Seoul, South Korea.
Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Theranostics. 2018 Feb 3;8(5):1389-1398. doi: 10.7150/thno.20706. eCollection 2018.
Cancer proteomics is the manifestation of relevant biological processes in cancer development. Thus, it reflects the activities of tumor cells, host-tumor interactions, and systemic responses to cancer therapy. To understand the causal effects of tumorigenesis or therapeutic intervention, longitudinal studies are greatly needed. However, most of the conventional mouse experiments are unlikely to accommodate frequent collection of serum samples with a large enough volume for multiple protein assays towards single-object analysis. Here, we present a technique based on magneto-nanosensors to longitudinally monitor the protein profiles in individual mice of lymphoma models using a small volume of a sample for multiplex assays. Drug-sensitive and -resistant cancer cell lines were used to develop the mouse models that render different outcomes upon the drug treatment. Two groups of mice were inoculated with each cell line, and treated with either cyclophosphamide or vehicle solution. Serum samples taken longitudinally from each mouse in the groups were measured with 6-plex magneto-nanosensor cytokine assays. To find the origin of IL-6, experiments were performed using IL-6 knock-out mice. The differences in serum IL-6 and GCSF levels between the drug-treated and untreated groups were revealed by the magneto-nanosensor measurement on individual mice. Using the multiplex assays and mouse models, we found that IL-6 is secreted by the host in the presence of tumor cells upon the drug treatment. The multiplex magneto-nanosensor assays enable longitudinal proteomic studies on mouse tumor models to understand tumor development and therapy mechanisms more precisely within a single biological object.
癌症蛋白质组学是癌症发展中相关生物学过程的表现。因此，它反映了肿瘤细胞的活动、宿主-肿瘤相互作用以及对癌症治疗的全身反应。为了了解肿瘤发生或治疗干预的因果效应，非常需要进行纵向研究。然而，大多数传统的小鼠实验不太可能频繁采集足够体积的血清样本，以进行针对单个对象的多次蛋白质分析。在这里，我们提出了一种基于磁纳米传感器的技术，该技术可使用小体积的样本进行多重分析，来纵向监测淋巴瘤模型中单个小鼠的蛋白质图谱。使用两种细胞系开发了对药物治疗有不同反应的癌症细胞系小鼠模型。每组小鼠接种两种细胞系之一，并分别用环磷酰胺或载体溶液处理。从每组小鼠中采集的血清样本进行 6-plex 磁纳米传感器细胞因子分析。为了找到 IL-6 的来源，使用 IL-6 敲除小鼠进行了实验。通过对个体小鼠进行磁纳米传感器测量，揭示了药物处理组和未处理组之间血清 IL-6 和 GCSF 水平的差异。使用多重分析和小鼠模型，我们发现，在药物治疗存在肿瘤细胞的情况下，宿主会分泌 IL-6。 该多重磁纳米传感器分析方法能够对小鼠肿瘤模型进行纵向蛋白质组学研究，从而更精确地了解肿瘤发展和治疗机制，而无需使用多个生物对象。
