Abstract 4314: A mouse model of cerebral cavernous malformations

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Cerebral cavernous malformations (CCM) are prevalent cerebral vascular lesions involving aberrant angiogenesis that can lead to hemorrhage, epilepsy, and other neurological manifestations. CCM consists of brittle, proliferating caverns filled with blood and lined with endothelial cells. However, the underlying mechanism of CCM development is poorly understood. The cytokine vascular endothelial cell growth inhibitor (VEGI; TNFSF15; TL1A) is an endogenous negative regulator of angiogenesis produced largely by endothelial cells and exerts a specific inhibitory activity on the proliferation of endothelial cells. We found that the production of VEGI by the endothelium is nearly completely diminished in the CCM tissues. In sharp contrast, the expression of VEGI is readily detectable on the vasculature in nearby brain tissues. On the other hand, angiogenic factors such as vascular endothelial cell growth factor (VEGF) is known to be highly expressed in CCM lesions. We show here that an imbalance of angiogenesis promoters and inhibitors, namely, the down-regulation of VEGI and up-regulation of VEGF, are attributable to the development of CCM. We have constructed a mouse CCM model by implanting mouse endothelial cell line bEnd3 cells in the brain of a female BALB/C mouse. The cavernous blood vessels formed in the model closely resemble those observed in CCM and thus may be used to study the pathology and treatment options of CCM. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4314. doi:10.1158/1538-7445.AM2011-4314