info:eu-repo/semantics/article
Heme oxygenase-1 expression in human gliomas and its correlation with poor prognosis in patients with astrocytoma
Fecha
2013-11Registro en:
Gandini, Norberto Ariel; Fermento, María Eugenia; Salomón, Débora Gisele; Obiol, Diego Javier; Andrés, Nancy Carolina; et al.; Heme oxygenase-1 expression in human gliomas and its correlation with poor prognosis in patients with astrocytoma; Springer; Tumor Biology; 35; 3; 11-2013; 2803-2815
1010-4283
Autor
Gandini, Norberto Ariel
Fermento, María Eugenia
Salomón, Débora Gisele
Obiol, Diego Javier
Andrés, Nancy Carolina
Zenklusen, Jean C.
Arevalo, Julian
Blasco, Jorge
Lopez, Alejandro
Facchinetti, Maria Marta
Curino, Alejandro Carlos
Resumen
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.