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BACKGROUND Increased expression of fibroblast activation protein (FAP) is characteristic for several cancer types including human glioblastomas (GBM). FAP is expressed on both cancer as well as stromal cells which were demonstrated in extracranial tumors to maintain a microenvironment permissive for tumor growth and thus to contribute to tumor progression. FAP is considered a potential diagnostic and therapeutic target and several approaches for its targeting have been recently developed. In this work, we investigated the role of FAP+ stromal cells in glioblastoma angiogenesis. MATERIAL AND METHODS Expression of FAP and other phenotypic markers was assessed by immunocytochemistry and immunohistochemistry. FAP+ stromal cells and primary microvascular endothelial cells were isolated using magnetic activated cell sorting (MACS). Genetic aberrations were assayed by comparative genomic hybridization/single-nucleotide polymorphism analysis. Angiogenesis was evaluated using a 3D spheroid-based sprouting assay and a chorioallantoic membrane assay. A cytokine array was used to analyze soluble mediators released by FAP+ stromal cells. RESULTS FAP+ stromal cells were predominantly localized around activated CD105+ endothelial cells and their quantity positively correlated with glioblastoma vascularization. FAP+ stromal cells derived from human GBMs had a mesenchymal phenotype, were non-tumorigenic and in most cases lacked cytogenetic aberrations characteristic of GBMs. Conditioned media derived from FAP+ stromal cells induced angiogenic sprouting of both macrovascular HUVEC as well as microvascular primary endothelial cells derived from human GBMs. In a chorioallantoic membrane assay, admixture of FAP+ stromal cells to glioma cells was associated with increased angiogenesis and more frequent occurrence of hemorrhages. Cytokine array revealed a significant disbalance between several proangiogenic and antiangiogenic mediators compared to normal pericytes, and an increased Angiopoietin 2/1 ratio in conditioned media from FAP+ stromal cells. CONCLUSION Our results bring new evidence that GBM associated FAP+ stromal cell promote angiogenesis by changing the balance between proangiogenic and antiangiogenic mediators and thus they may contribute to glioblastoma progression. ACKNOWLEDGEMENT Supported by Progres Q28/1LFUK and grant LM2015064 of the EATRIS-CZ and the Center for Tumor Ecology (CZ.02.1.01/0.0/0.0/16_019/0000785).

P16.12 Proangiogenic effect of fibroblast activation protein positive stromal cells derived from human glioblastomas