2026-06-14T02:29:04Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/119462025-06-13T09:02:17Zcom_20.500.12105_15322com_20.500.12105_2051com_20.500.12105_2052col_20.500.12105_16938col_20.500.12105_16974col_20.500.12105_19617

00925njm 22002777a 4500 dc Segura-Collar, Berta author Garranzo-Asensio, Maria author Herranz, Beatriz author Hernandez-SanMiguel, Esther author Cejalvo, Teresa author Casas, Bárbara S author Matheu, Ander author Pérez-Núñez, Ángel author Sepúlveda-Sánchez, Juan Manuel author Hernández-Laín, Aurelio author Palma, Verónica author Gargini, Ricardo author Sánchez-Gómez, Pilar author 2021-02-16 The extraordinary plasticity of glioma cells allows them to contribute to different cellular compartments in tumor vessels, reinforcing the vascular architecture. It was recently revealed that targeting glioma-derived pericytes, which represent a big percentage of the mural cell population in aggressive tumors, increases the permeability of the vessels and improves the efficiency of chemotherapy. However, the molecular determinants of this transdifferentiation process have not been elucidated. Here we show that mutations in epidermal growth factor receptor (EGFR) stimulate the capacity of glioma cells to function as pericytes in a BMX (bone marrow and X-linked) and SOX9-dependent manner. Subsequent activation of platelet-derived growth factor receptor beta (PDGFRβ) in the vessel walls of EGFR mutant gliomas stabilized the vasculature and facilitated the recruitment of immune cells. These changes in the tumor microenvironment conferred a growth advantage to the tumors but also rendered them sensitive to pericyte-targeting molecules such as ibrutinib or sunitinib. In the absence of EGFR mutations, high-grade gliomas were enriched in blood vessels but showed a highly disrupted blood-brain-barrier due to the decreased BMX/SOX9 activation and pericyte coverage, which led to poor oxygenation, necrosis, and hypoxia. Overall, these findingds identify EGFR mutations as key regulators of the glioma-to-pericyte transdifferentiation, highlighting the intricate relationship between the tumor cells and their vascular and immune milieu. Our results lay the foundations for a vascular-dependent stratification of gliomas and suggest different therapeutic vulnerabilities determined by the genetic status of EGFR. Cancer Res . 2021 Feb 16;canres.3558.2020 10.1158/0008-5472.CAN-20-3558 1538-7445 Cancer research 33593822 http://hdl.handle.net/20.500.12105/11946 Glioma EGFR Pericytes Blood-brain barrier (BBB) Tumor-microenvironment (TME) Immune infiltrate Tumor-derived pericytes driven by EGFR mutations govern the vascular and immune microenvironment of gliomas