2026-06-14T05:05:18Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/78322024-11-29T22:47:14Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Ullrich, Martin author Richter, Susan author Seifert, Verena author Hauser, Sandra author Calsina, Bruna author Martínez-Montes, Ángel M author Ter Laak, Marjolein author Ziegler, Christian G author Timmers, Henri author Eisenhofer, Graeme author Robledo Batanero, Mercedes author Pietzsch, Jens author 2019-05-28 Cyclooxygenase 2 (COX-2) is a key enzyme of the tumorigenesis-inflammation interface and can be induced by hypoxia. A pseudohypoxic transcriptional signature characterizes pheochromocytomas and paragangliomas (PPGLs) of the cluster I, mainly represented by tumors with mutations in von Hippel-Lindau (VHL), endothelial PAS domain-containing protein 1 (EPAS1), or succinate dehydrogenase (SDH) subunit genes. The aim of this study was to investigate a possible association between underlying tumor driver mutations and COX-2 in PPGLs. COX-2 gene expression and immunoreactivity were examined in clinical specimens with documented mutations, as well as in spheroids and allografts derived from mouse pheochromocytoma (MPC) cells. COX-2 in vivo imaging was performed in allograft mice. We observed significantly higher COX-2 expression in cluster I, especially in VHL-mutant PPGLs, however, no specific association between COX-2 mRNA levels and a hypoxia-related transcriptional signature was found. COX-2 immunoreactivity was present in about 60% of clinical specimens as well as in MPC spheroids and allografts. A selective COX-2 tracer specifically accumulated in MPC allografts. This study demonstrates that, although pseudohypoxia is not the major determinant for high COX-2 levels in PPGLs, COX-2 is a relevant molecular target. This potentially allows for employing selective COX-2 inhibitors as targeted chemotherapeutic agents and radiosensitizers. Moreover, available models are suitable for preclinical testing of these treatments. Cancers (Basel). 2019 ;11(6). pii: E743. 10.3390/cancers11060743 2072-6694 Cancers 31142060 http://hdl.handle.net/20.500.12105/7832 EPAS1 NF1 VHL Fluorescence imaging Hypoxia-inducible factor Immunohistochemistry Inflammation Mouse pheochromocytoma cells Radiosensitization Succinate dehydrogenase Targeting Cyclooxygenase-2 in Pheochromocytoma and Paraganglioma: Focus on Genetic Background