Abstract 1197: Soluble uPAR plays a critical role in the progression of meningioma by autocrine signaling

Abstract

Abstract In previous studies, we have reported on the vital role of the uPA-uPAR system in the progression of meningioma. Recent studies on the molecular structure of uPAR confirm that its shedding characterizes a further level of regulation in cellular processes. Here, we show that malignant meningioma cells release higher levels of soluble uPAR (SuPAR). Further, SuPAR concentration increased with radiation treatment (7 Gy) while uPAR knockdown diminished it. Deglycosylation analysis illustrated the existence of both SuPAR and cleaved SuPAR in vitro and in vivo. The cells shed SuPAR and phospholipase C mediates radiation-induced shedding of uPAR. SuPAR had a physical interaction with uPA and influences its activity in a concentration-dependent manner. Nonetheless, SuPAR did not adversely influence cell proliferation or cell cycle characteristics, but instead activated the MEK- ERK pathway. Receptor tyrosine kinase arrays and function blocking assays revealed the role of FPRL 1 receptors in SuPAR-mediated signaling. Further, SuPAR acted as a chemo-attractant for the invasion and migration of meningioma cells. Tumor bearing mice showed a significant rise in serum SuPAR concentrations, which also correlated with radiation treatment and morbidity. In conclusion, our results demonstrate the pro-invasive role and prognostic significance of SuPAR in the progression of meningioma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1197. doi:1538-7445.AM2012-1197