P10.13.A AN ATRAUMATIC ACCESS TO HUMAN GLIOBLASTOMA IN A XENOGRAFT ANIMAL MODEL BY CEREBRAL OPEN FLOW MICROPERFUSION FOR THE ASSESSMENT OF BIOMARKER IN THE TUMOR MICROENVIRONMENT

Abstract

Abstract BACKGROUND Orthotopic xenograft studies strongly promote the development of targeted/personalized cancer therapies to improve the still poor life expectancy of glioblastoma patients. In recent years, the tumor microenvironment has increasingly become subject of investigations, as it could have an impact on the progression of the cancer. However, examination of the tumor microenvironment with currently available methods inevitably causes trauma that might compromise the reliability of the obtained data. We aimed to implement an atraumatic access to human glioblastoma with cerebral Open Flow Microperfusion (cOFM) by implantation of xenograft cells in rodent’s brain of different species (mouse and rat) with intact blood brain barrier (BBB) and subsequent development of a xenograft glioblastoma at the interface between the cOFM probe and the surrounding brain tissue. Thereafter, we used the cOFM probe to collect interstitial fluid (ISF) from the tumor microenvironment for metabolome and biomarker assessment. MATERIAL AND METHODS Human glioma cells were implanted at a well-defined position into immune-deficient rodent’s brain via cOFM or syringe. Characteristics of the mature tumors from both groups were assessed. ISF from tumor microenvironment was collected without further traumatization by using cOFM, and the collected tumor ISF samples were analyzed using a UHPLC-HRMS metabolomics platform. A targeted (Biocrates MxP®) and an untargeted (Metaboanalyst) approach were used to analyze the metabolomics data. RESULTS For the first time xenograft cells were successfully introduced into rodent brain with intact BBB using cOFM, and the tumor tissue that developed around the cOFM probe was unaffected by the presence of the probe. Thereby, an atraumatic access to the tumor was created. The mature cOFM-induced tumors resembled the syringe-induced ones and showed typical features of human glioblastoma. The cOFM sampling procedure did not alter tumor morphology. CONCLUSION This novel atraumatic access to human glioblastoma in a rodent brain was used to collect ISF from functional tumor microenvironment in vivo without trauma generation. The thereby generated reliable data are likely to promote drug research, biomarker identification, and enable investigation of the BBB of a functional tumor.