Longitudinal multiplexed measurement of quantitative proteomic signatures in mouse lymphoma models using magneto-nanosensors

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. Methods: 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. Results: 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. Conclusion: 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.We would like to thank Drs. D. Mitchell Magee and Joshua LaBaer at Arizona State University for their helpful discussions. This work was supported by Physical Science Oncology Center (U54CA143907), Center for Cancer Nanotechnology Excellence (U54CA151459 and U54CA199075), and the National Research Foundation of Korea (NRF) grant funded by the Korea government (NRF-2017R1C1B5076529). I.A. was supported by Dr. Mildred Scheel postdoctoral fellowship (project no. 109902) of the German Cancer Aid (Deutsche Krebshilfe)