Abstract 4145: Brain-derived endothelial cells stimulate migration of different human, mouse, and rat glioma cell lines in vivo and in vitro

Abstract

Abstract Glioblastoma multiforme (GBM) is the most lethal of the human brain tumors. Despite intensive chemotherapy, radiotherapy and surgery, patients usually die within 1-2 years of diagnosis. Glioma cells display the remarkable capacity to infiltrate the brain. They diffusely invade the brain by active cell migration either along blood vessels, white matter tracts, interstitially, or surrounding the meninges. We identified a number of glioma cells (including glioma stem cells) from mouse and human which migrate primarily along the vasculature. Molecular determinants that attract glioma cells to blood vessels remain poorly understood; inhibition of glioma growth along blood vessels could be a potential treatment strategy for GBM. In the present study, we studied whether brain-derived endothelial cells alone, or in combination with other brain cell types attract glioma cells. To do so we tested the ability of human and mouse brain-derived endothelial cells to stimulate the migration of human, mouse and rat-derived glioma cell lines in an in vitro migration assay. We tested the migration of different primary human glioma cell lines like HF2303, MGG8, MSP-12, IN859, IN2045 and U251 in response to mouse brain-derived endothelial (MBVE) cells and mixed mouse brain cells (MMB). Of these, HF2303, MSP-12 cells showed significant migration but not MGG8, IN859, IN2045 and U251 cell lines. Further, Gl26-cit, a mouse glioma and CNS1-cit a rat cell line also exhibited significant migration towards MBVE as well as MMB cells. These results are in line with our in vivo data showing that HF2303, and Gl26-cit, but not MGG8 cells, invade along the blood vessels. Differential migration of various human glioma cell lines in response to MBVE cells is probably due to their heterogeneous growth patterns in vivo. Interestingly, our in vitro data showed that the mouse endothelial cells together with mouse astrocytes, another brain cell type, promote the migration of Gl26-cit cells to a greater extent than the mouse endothelial cells alone. In summary, the behavior of glioma cells in vitro is consistent with their migration patterns in vivo. Further, other brain cell types like astrocytes along with MBVE cells enhance migration of glioma cells. Therefore, we are now using this in vitro model to discover the molecular mechanisms responsible for glioma growth towards blood vessels. This work was supported by NIH-NINDS, the Department of Neurosurgery, and very generous support from Phil F. Jenkins. Citation Format: Viveka N. Yadav, Gregory J. Baker, Samanthi Narayanan, Maria G. Castro, Pedro R. Lowenstein. Brain-derived endothelial cells stimulate migration of different human, mouse, and rat glioma cell lines in vivo and in vitro. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4145. doi:10.1158/1538-7445.AM2015-4145