10180- ANGI-5 COMPREHENSIVE ANALYSIS OF MECHANISM OF INVASION AND DISSEMINATION FOR MALIGNANT BRAIN TUMOR USING XENOGRAFT MODELS

Abstract BACKGROUND Malignant brain tumors are frequently resistant to current treatments and have a poor prognosis. Many malignant brain tumors invade the surrounding brain tissue and/or show leptomeningeal metastasis when they recur. Thus, elucidating the mechanisms of invasion and leptomeningeal metastasis is important to improve the prognosis of malignant brain tumors. In this study, we comprehensively analyzed the mechanisms of invasion and leptomeningeal metastasis of malignant brain tumors using mouse xenograft models. METHODS Patient derived glioblastoma cells (GDC519) and breast cancer cell line, MDA-MB-231, were labeled with GFP and luciferase. GDC519 were transplanted into the right cerebral cortex of immunodeficient mice and when the mice got tumors, the right and left cerebrum were dissected separately. We sorted tumor cells by flow cytometry and extracted RNA from tumor cells in right and left cerebrum, respectively. We performed RNA sequencing and analyzed the transcriptome differences. On the other hand, MDA-MB-231 cells were injected into the right ventricle of immunodeficient mice. Tumor cells from cerebrospinal fluid, and spinal cords were sorted and analyzed the transcriptome differences by RNA sequencing. RESULTS In the model in which GDC519 was transplanted, we found significant differences in expressions of extracellular matrix related proteins, cell motility related proteins, and cell adhesion related proteins between tumor cells in right and left cerebrum. In addition, in the model in which MDA-MB-231 was transplanted into the right ventricle, we found significant differences in expressions of extracellular matrix related proteins and PI3K-Akt signaling pathway related proteins between tumor cells from cerebrospinal fluid and spinal cord. CONCLUSION These results suggest that it would be possible to identify molecules involved in the invasion and leptomeningeal metastasis of malignant brain tumors using a mouse xenograft model. Further studies are necessary to examine the functional role of these genes in invasion and leptomeningeal metastasis.