title: VEGFR-2 Expression in Glioblastoma Multiforme Depends on Inflammatory Tumor Microenvironment.
abstract: Glioblastoma multiforme (GBM) is one of the most angiogenic tumors. However, antiangiogenic therapy has not shown significant clinical efficacy. The aim of our study was to evaluate the impact of inflammatory tumor microenvironment on the expression of vascular endothelial growth factor receptor 2 (VEGFR-2). Surgically excised primary GBM tissues were histologically examined for overall extent of inflammation (score 1-3). After immunohistochemistry, the tissue expression of ICAM-1 (optical density), the number of VEGFR-2 positive (VEGFR-2+) blood vessels (per microscopic field), and the endothelial staining intensity of VEGFR-2 (score 0-3) were determined. In GBM, the extent of inflammation was 1.9 ± 0.7 (group mean ± SD). Mean optical density of inflammatory mediator ICAM-1 was 57.0 ± 27.1 (pixel values). The number of VEGFR-2+ blood vessels and endothelial VEGFR-2 staining intensity were 6.2 ± 2.4 and 1.2 ± 0.8, respectively. A positive association was found between endothelial VEGFR-2 staining intensity and the extent of inflammation (p = 0.005). Moreover, VEGFR-2 staining intensity correlated with the expression level of ICAM-1 (p = 0.026). The expression of VEGFR-2, one of the main targets of antiangiogenic therapy, depends on GBM microenvironment. Higher endothelial VEGFR-2 levels were seen in the presence of more pronounced inflammation. Target dependence on inflammatory tumor microenvironment has to be taken into consideration when treatment approaches that block VEGFR-2 signaling are designed.
authors.affiliation: Hematology and Oncology Clinic, Department of Radiotherapy and Oncological Therapy, Tartu University Hospital, 51003 Tartu, Estonia; Faculty of Medicine, University of Tartu, 50411 Tartu, Estonia.
authors.forename: Jana
authors.initials: J
authors.lastname: Jaal
authors.affiliation: Hematology and Oncology Clinic, Department of Radiotherapy and Oncological Therapy, Tartu University Hospital, 51003 Tartu, Estonia; East-Tallinn Central Hospital, Center of Oncology, 10138 Tallinn, Estonia.
authors.forename: Marju
authors.initials: M
authors.lastname: Kase
authors.affiliation: Faculty of Medicine, University of Tartu, 50411 Tartu, Estonia.
authors.forename: Ave
authors.initials: A
authors.lastname: Minajeva
authors.affiliation: Faculty of Medicine, University of Tartu, 50411 Tartu, Estonia.
authors.forename: Mikk
authors.initials: M
authors.lastname: Saretok
authors.affiliation: Faculty of Medicine, University of Tartu, 50411 Tartu, Estonia.
authors.forename: Aidi
authors.initials: A
authors.lastname: Adamson
authors.affiliation: Faculty of Medicine, University of Tartu, 50411 Tartu, Estonia.
authors.forename: Jelizaveta
authors.initials: J
authors.lastname: Junninen
authors.affiliation: Faculty of Medicine, University of Tartu, 50411 Tartu, Estonia.
authors.forename: Tõnis
authors.initials: T
authors.lastname: Metsaots
authors.affiliation: Hematology and Oncology Clinic, Department of Radiotherapy and Oncological Therapy, Tartu University Hospital, 51003 Tartu, Estonia.
authors.forename: Tõnu
authors.initials: T
authors.lastname: Jõgi
authors.affiliation: Hematology and Oncology Clinic, Department of Radiotherapy and Oncological Therapy, Tartu University Hospital, 51003 Tartu, Estonia.
authors.forename: Madis
authors.initials: M
authors.lastname: Joonsalu
authors.affiliation: Hematology and Oncology Clinic, Department of Radiotherapy and Oncological Therapy, Tartu University Hospital, 51003 Tartu, Estonia.
authors.forename: Markus
authors.initials: M
authors.lastname: Vardja
authors.affiliation: Faculty of Medicine, University of Tartu, 50411 Tartu, Estonia; Neurology Clinic, Department of Neurosurgery, Tartu University Hospital, 51014 Tartu, Estonia.
authors.forename: Toomas
authors.initials: T
authors.lastname: Asser