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Tumor Biology
Published in: Tumor Biology 3/2014

01-03-2014 | Research Article

Heme oxygenase-1 expression in human gliomas and its correlation with poor prognosis in patients with astrocytoma

Authors: Norberto A. Gandini, María E. Fermento, Débora G. Salomón, Diego J. Obiol, Nancy C. Andrés, Jean C. Zenklusen, Julián Arevalo, Jorge Blasco, Alejandro López Romero, María M. Facchinetti, Alejandro C. Curino

Published in: Tumor Biology | Issue 3/2014

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Abstract

In human glioma tumors, heme oxygenase-1 (HO-1) has been shown to be upregulated both when compared with normal brain tissues and also during oligodendroglioma progression. The cell types that express HO-1 have been shown to be mainly macrophages/microglia and T cells. However, many other reports also demonstrated that cell lines derived from glioma tumors and astrocytes express HO-1 after the occurrence of a wide variety of cell injuries and stressors. In addition, the significance of HO-1 upregulation in glioma had not, so far, been addressed. We therefore aimed at investigating the expression and significance of HO-1 in human glial tumors. For this purpose, we performed a wide screening of HO-1 expression in gliomas by using tissue microarrays containing astrocytomas, oligodendrogliomas, mixed tumors, and normal brain tissues. We subsequently correlated protein expression with patient clinicopathological data. We found differences in HO-1 positivity rates between non-malignant brain (22 %) and gliomas (54 %, p = 0.01). HO-1 was expressed by tumor cells and showed cytoplasmic localization, although 19 % of tumor samples also depicted nuclear staining. Importantly, a significant decrease in the overall survival time of grade II and III astrocytoma patients with HO-1 expression was observed. This result was validated at the mRNA level in a cohort of 105 samples. However, no association of HO-1 nuclear localization with patient survival was detected. In vitro experiments aimed at investigating the role of HO-1 in glioma progression showed that HO-1 modulates glioma cell proliferation, but has no effects on cellular migration. In conclusion, our results corroborate the higher frequency of HO-1 protein expression in gliomas than in normal brain, demonstrate that HO-1 is expressed by glial malignant cells, and show an association of HO-1 expression with patients’ shorter survival time.
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Metadata
Title
Heme oxygenase-1 expression in human gliomas and its correlation with poor prognosis in patients with astrocytoma
Authors
Norberto A. Gandini
María E. Fermento
Débora G. Salomón
Diego J. Obiol
Nancy C. Andrés
Jean C. Zenklusen
Julián Arevalo
Jorge Blasco
Alejandro López Romero
María M. Facchinetti
Alejandro C. Curino
Publication date
01-03-2014
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 3/2014
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-013-1373-z

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