Abstract LB-317: Use of in vivo microdialysis to evaluate biomarker levels in the tumor and tumor free flank of freely-moving PDX mice

Abstract

The tumor microenvironment (TME) constitutes unique surroundings where cancer cells communicate with one another and with the host immune system by releasing a multitude of factors. Information about the physiological state of the TME can help in gaining a broader understanding of cancer biology and developing novel cancer therapeutics. Previous work has demonstrated the ability to use in vivo microdialysis to monitor the release of adenosine and its metabolites from murine cancer models. To further these findings, we used in vivo microdialysis to measure biomarkers in the patient-derived xenograft (PDX) cancer model. By using human tumor tissue models, we aim to bridge the gap between rodent models and human tumors to help develop better cancer therapeutics. The current set of studies used microdialysis in different PDX lines representing human tumor models (provided by CRL DRS Freiburg). Xenograft growth was monitored and upon a tumor volume > 400 mm3, the animals underwent surgical implantation of microdialysis probes in the tumor and the tumor-free flank. The implanted probes were perfused with dialysate fluid and samples from the both flanks were continuously collected over several hours. Levels of ATP, inosine and kynurenine metabolites were quantified by EIA or LC-MS/MS analysis. Analysis of microdialysate samples from tumor and tumor-free flank demonstrated differences in analyte levels between the two sampling sites within one animal indicating that the levels of ATP and metabolites measured in PDX tumors is unique to the tumor microenvironment. In addition, the various PDX models showed differences in biomarker levels between the different tumor types. There is a wide range of biomarkers which are important indicators of energy consumption and provide an insight in the differences in metabolic activity between the different xenografts. Moreover, these data demonstrate that microdialysis can be used to test targeted therapies and follow relevant biomarker levels over time. Thereby, providing better insight in effects of new therapeutic treatments within the patient specific tumor tissue itself. Citation Format: Mariette Heins, Loreen Weichert, Sabine Gorynia, Gunnar Flik, Arash Rassoulpour. Use of in vivo microdialysis to evaluate biomarker levels in the tumor and tumor free flank of freely-moving PDX mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-317.