VEGFR-2 Expression in Glioblastoma Multiforme Depends on Inflammatory Tumor Microenvironment

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 (...

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Main Authors: Jana Jaal, Marju Kase, Ave Minajeva, Mikk Saretok, Aidi Adamson, Jelizaveta Junninen, Tõnis Metsaots, Tõnu Jõgi, Madis Joonsalu, Markus Vardja, Toomas Asser
Format: Article
Language:English
Published: Wiley 2015-01-01
Series:International Journal of Inflammation
Online Access:http://dx.doi.org/10.1155/2015/385030
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author Jana Jaal
Marju Kase
Ave Minajeva
Mikk Saretok
Aidi Adamson
Jelizaveta Junninen
Tõnis Metsaots
Tõnu Jõgi
Madis Joonsalu
Markus Vardja
Toomas Asser
author_facet Jana Jaal
Marju Kase
Ave Minajeva
Mikk Saretok
Aidi Adamson
Jelizaveta Junninen
Tõnis Metsaots
Tõnu Jõgi
Madis Joonsalu
Markus Vardja
Toomas Asser
author_sort Jana Jaal
collection DOAJ
description 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.
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spelling doaj-art-3144e164afa94a27a6efb7f0baf4ecba2025-02-03T01:00:04ZengWileyInternational Journal of Inflammation2090-80402042-00992015-01-01201510.1155/2015/385030385030VEGFR-2 Expression in Glioblastoma Multiforme Depends on Inflammatory Tumor MicroenvironmentJana Jaal0Marju Kase1Ave Minajeva2Mikk Saretok3Aidi Adamson4Jelizaveta Junninen5Tõnis Metsaots6Tõnu Jõgi7Madis Joonsalu8Markus Vardja9Toomas Asser10Hematology and Oncology Clinic, Department of Radiotherapy and Oncological Therapy, Tartu University Hospital, 51003 Tartu, EstoniaHematology and Oncology Clinic, Department of Radiotherapy and Oncological Therapy, Tartu University Hospital, 51003 Tartu, EstoniaFaculty of Medicine, University of Tartu, 50411 Tartu, EstoniaFaculty of Medicine, University of Tartu, 50411 Tartu, EstoniaFaculty of Medicine, University of Tartu, 50411 Tartu, EstoniaFaculty of Medicine, University of Tartu, 50411 Tartu, EstoniaFaculty of Medicine, University of Tartu, 50411 Tartu, EstoniaHematology and Oncology Clinic, Department of Radiotherapy and Oncological Therapy, Tartu University Hospital, 51003 Tartu, EstoniaHematology and Oncology Clinic, Department of Radiotherapy and Oncological Therapy, Tartu University Hospital, 51003 Tartu, EstoniaHematology and Oncology Clinic, Department of Radiotherapy and Oncological Therapy, Tartu University Hospital, 51003 Tartu, EstoniaFaculty of Medicine, University of Tartu, 50411 Tartu, EstoniaGlioblastoma 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.http://dx.doi.org/10.1155/2015/385030
spellingShingle Jana Jaal
Marju Kase
Ave Minajeva
Mikk Saretok
Aidi Adamson
Jelizaveta Junninen
Tõnis Metsaots
Tõnu Jõgi
Madis Joonsalu
Markus Vardja
Toomas Asser
VEGFR-2 Expression in Glioblastoma Multiforme Depends on Inflammatory Tumor Microenvironment
International Journal of Inflammation
title VEGFR-2 Expression in Glioblastoma Multiforme Depends on Inflammatory Tumor Microenvironment
title_full VEGFR-2 Expression in Glioblastoma Multiforme Depends on Inflammatory Tumor Microenvironment
title_fullStr VEGFR-2 Expression in Glioblastoma Multiforme Depends on Inflammatory Tumor Microenvironment
title_full_unstemmed VEGFR-2 Expression in Glioblastoma Multiforme Depends on Inflammatory Tumor Microenvironment
title_short VEGFR-2 Expression in Glioblastoma Multiforme Depends on Inflammatory Tumor Microenvironment
title_sort vegfr 2 expression in glioblastoma multiforme depends on inflammatory tumor microenvironment
url http://dx.doi.org/10.1155/2015/385030
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