RRC ID 39063
Author Nakashima S, Sugita Y, Miyoshi H, Arakawa F, Muta H, Ishibashi Y, Niino D, Ohshima K, Terasaki M, Nakamura Y, Morioka M.
Title Endothelin B receptor expression in malignant gliomas: the perivascular immune escape mechanism of gliomas.
Journal J. Neurooncol.
Abstract In order to clarify the role of endothelin B receptors (ETBRs) in gliomas, we analyzed cell cultures and surgical specimens of gliomas using RT-PCR and immunohistochemistry. RT-PCR measured the absolute expression of ETBR mRNA in twelve samples, which included gliomas that were classified using the World Health Organization (WHO) classification system Grade I-IV, as well as two glioblastoma cell lines (CCF-STTG1 and U87-MG). Using immunohistochemistry, 77 glioma specimens were evaluated for their expression of ETBR and infiltrating T lymphocytes, including an analysis of cytotoxic T cells (CTLs) and regulatory T lymphocytes (Tregs). The number of ETBR-positive vessels in the glioblastomas (Grade IV) was significantly higher than in other grades of gliomas (comparisons to Grade IV, Grade I: p = 0.0323, Grade II: p = 0.0009, Grade III: p = 0.0273). The ETBR expression rate (defined as the number of ETBR-positive blood vessels divided by the total number of blood vessels) in the glioblastomas was higher than the ETBR expression rate in the low-grade gliomas (compared to Grade IV, Grade I: p = 0.0132, Grade II: p = 0.0018, Grade III: p = 0.0745). In addition, the cases which had an ETBR expression rate of 50 % or higher exhibited fewer infiltrating CTLs and more infiltrating Tregs compared to the cases with an ETBR expression rate <50 % (CTLs: p = 0.0342; Tregs: p = 0.0175). Isocitrate dehydrogenase 1 (IDH-1) mutations were identified in 21 cases, but there was no correlation between ETBR expression and IDH-1 mutations for any WHO grade. These results suggest that ETBR expression during neo-angiogenesis may interfere with the homing of CTLs around the tumor and be involved in the immune escape mechanism of gliomas.
Volume 127(1)
Pages 23-32
Published 2016-3
DOI 10.1007/s11060-015-2017-5
PII 10.1007/s11060-015-2017-5
PMID 26645886
MeSH Biomarkers, Tumor / genetics Biomarkers, Tumor / metabolism* Blotting, Western Brain Neoplasms / genetics Brain Neoplasms / immunology Brain Neoplasms / metabolism Brain Neoplasms / pathology* Gene Expression Regulation, Neoplastic Glioma / genetics Glioma / immunology Glioma / metabolism Glioma / pathology* Humans Immunoenzyme Techniques Isocitrate Dehydrogenase / genetics Mutation / genetics Neoplasm Grading Neovascularization, Pathologic* RNA, Messenger / genetics Real-Time Polymerase Chain Reaction Receptor, Endothelin B / genetics Receptor, Endothelin B / metabolism* Reverse Transcriptase Polymerase Chain Reaction T-Lymphocytes, Cytotoxic / immunology* Tumor Cells, Cultured
IF 3.129
Times Cited 3
Human and Animal Cells CCF-STTG1(RCB1977)