LRP1 and Angiogenesis in Pediatric Malignant Glioma

Background
Malignant glioma accounts for a significant amount of morbidity and mortality among children with brain tumors. However, there are still no curable therapies. The abnormally accelerated blood vessel formation is thought to be a key pathogenic event in malignant glioma.

Blood vessels are composed of endothelial cells and vascular mural cells (i.e. pericytes and vascular smooth muscle cells), both of which are differentiated from vascular precursor cells. Therefore, we focus on the differentiation of vascular precursor cells to endothelial cells and pericytes for better understanding of how malignant glioma is developed. Our recent results have demonstrated that low-density lipoprotein receptor-related protein 1 (LRP1) mediates brain vessel formation. Thus, we hypothesize that LRP1 mediates the differentiation of vascular precursor cells as well as controls vascular formation, which might be involved in malignant glioma pathogenesis. In this proposed study, we will use the induced pluripotent stem (iPS) cells to examine the differentiation of vascular precursor cells, which is the cutting edge of life science.

Significance Our innovative approach will likely provide a novel therapeutic target against childhood brain cancers. If successful, our study will reveal that modulation of LRP1 function in blood vessels could be a new treatment for malignant glioma. Our ultimate goal is to conduct clinical trials to prevent abnormally accelerated vascular formation in malignant glioma through collaboration with clinicians. Thus, from the perspective of future translational research and the needs to develop novel therapy for childhood brain cancer, this project is highly significant and unique.