Heme oxygenase-1 expression in human gliomas  and its correlation with poor prognosis  in patients with astrocytoma.
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.
Norberto A
NA
Gandini
María E
ME
Fermento
Débora G
DG
Salomón
Diego J
DJ
Obiol
Nancy C
NC
Andrés
Jean C
JC
Zenklusen
Julián
J
Arevalo
Jorge
J
Blasco
Alejandro
A
López Romero
María M
MM
Facchinetti
Alejandro C
AC
Curino
D001254:Astrocytoma / Q000201:enzymology / Q000401:mortality / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis*; D001932:Brain Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D005455:Fluorescent Antibody Technique; D005910:Glioma / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D051547:Heme Oxygenase-1 / Q000032:analysis / Q000096:biosynthesis*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1