ANGI-16: IN VIVO AND IN VITRO STUDIES SHOW THAT BRAIN DERIVED ENDOTHELIAL CELLS STIMULATE MIGRATION OF HUMAN, MOUSE AND RAT GLIOMA CELLS

Glioblastoma multiforme (GBM) is the most lethal of human brain tumors. Glioma cells invade the brain by active migration along blood vessels, white matter tracts, interstitially, or surrounding the meninges. Molecular determinants of glioma migration patterns, i.e., those that attract glioma cells to blood vessels remain partially understood. We observed that several mouse and human glioma cells migrate primarily along the blood vasculature. Here, we tested the ability of human and mouse brain-derived endothelial (MBVE) cells to stimulate the migration of human, mouse and rat-derived glioma cell lines in an in vitro migration assay. Among different primary human glioma cell lines, HF2303 and MSP-12 cells showed significant directional migration while MGG8, IN859, IN2045 and U251 cells did not. Further, Gl26-cit, a mouse glioma and CNS1-cit a rat cell line also exhibited significant migration towards MBVE. These results were in line with our in vivo data wherein HF2303, and Gl26-cit, but not MGG8 cells, invaded mainly along blood vessels. Differential migration of various human glioma cell lines in response to MBVE cells in vitro is probably related to their growth patterns in vivo. To decipher the mechanism of GBM cell migration, we tested the role of various chemokines using in vitro migration assays. The migration of Gl26-cit and HF2303 towards MBVE were significantly inhibited by AMD3100, an inhibitor of CXCR4. Lastly, MBVE together with mouse astrocytes promote the in vitro migration of Gl26-cit cells to a greater extent than MBVE alone. In summary, the behavior of glioma cells in vitro is consistent with their migration patterns in vivo and therefore, using in vitro migration models are a good tool to identify molecular mechanisms responsible for glioma cell growth towards blood vessels. The CXCL12-CXCR4 signaling was found to be critical for the migration of both mouse and human glioma cell lines.