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Nonspecific expression of the angiogenesis gene BTG1 in glioblastoma
1  Faculty of Psychology , Universidad Nacional de Educación a Distancia (UNED), Madrid, 28040, Spain
Academic Editor: Allison B. Reiss

Abstract:

Disturbances in oxygen concentration, particularly hypoxia, occur in different pathological conditions, as in tumors, and hypoxia can also cause brain damage in strokes. One tissue response to low oxygen levels is the activation of angiogenesis. In glioblastoma, the most common primary brain tumor in adults, with a poor prognosis, microvascular proliferation in response to hypoxia is common. The Public Ivy Glioblastoma Atlas Project – Allen Institute for Brain Science contains an expression data set for 37 genes enriched in glioblastoma, and we have verified that at least 5 (ADGRL4, BTG1, ENPEP, ESM1, and STC1) are directly involved in angiogenesis. This study aims to investigate mRNA levels of these genes in different histologically-defined glioblastoma regions. To better compare the results obtained from in situ hybridization (ISH) in glioblastoma blocks, we selected images with a similar tissue architecture, specifically perinecrotic pseudopalisading regions with an underlying zone of a cellular tumor. Our primary results show that ADGRL4, ENPEP, ESM1, and STC1 genes were mainly expressed (in medium-high levels) in the endothelium of hyperplastic blood vessels that accumulated near the pseudopalisading cells. Nevertheless, the BTG1 gene (the protein that positively regulates endothelial cell differentiation and angiogenesis) was ubiquitously expressed (also at medium-high levels), both in the previous vessel regions and in the pseudopalisading around necrosis areas and the rest of the tumor. We used DDR1 as a control gene that is not expressed in endothelial cells. Our preliminary data also suggest a similar spatial distribution of ADGRL4, BTG1, ENPEP, ESM1, and STC1 expression in patients with different molecular subtypes of glioblastoma: classical, proneural, classical-mesenchymal, and neural-proneural. We conclude that ADGRL4, ENPEP, ESM1, and STC1 genes appear to be preferentially expressed in the endothelium of the glioblastoma microvasculature; however, BTG1 appears to show a ubiquitous distribution within the tumor. The functional significance and possible therapeutic relevance remain to be demonstrated.

Keywords: Glioblastoma; hypoxia; angiogenesis; BTG1; structures

 
 
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