Heme oxygenase-1 expression in human gliomas and its correlation with poor prognosis in patients with astrocytoma
| Autor: | Norberto Ariel Gandini, María Eugenia Fermento, Jean C. Zenklusen, Julián Arévalo, Débora Gisele Salomón, Jorge Alejandro Blasco, Alejandro López Romero, Maria Marta Facchinetti, Alejandro Carlos Curino, Diego Javier Obiol, Nancy Carolina Andrés |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Pathology
medicine.medical_specialty Cell type CIENCIAS MÉDICAS Y DE LA SALUD Survival Immunoblotting Fluorescent Antibody Technique Kaplan-Meier Estimate Biology Astrocytoma Real-Time Polymerase Chain Reaction Glioma Biomarkers Tumor medicine Humans Tissue microarray Microglia Brain Neoplasms Patología General Medicine purl.org/becyt/ford/3.1 [https] Prognosis medicine.disease Immunohistochemistry nervous system diseases Heme oxygenase Medicina Básica medicine.anatomical_structure Tissue Array Analysis purl.org/becyt/ford/3 [https] Oligodendroglioma Tissue Microarray Heme Oxygenase-1 |
| Zdroj: | CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas instacron:CONICET |
| Popis: | 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. Fil: Gandini, Norberto Ariel. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Bahia Blanca. Instituto de Invest.bioquimicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; Argentina Fil: Fermento, María Eugenia. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Bahia Blanca. Instituto de Invest.bioquimicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; Argentina Fil: Salomón, Débora Gisele. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Bahia Blanca. Instituto de Invest.bioquimicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; Argentina Fil: Obiol, Diego Javier. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Bahia Blanca. Instituto de Invest.bioquimicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; Argentina Fil: Andrés, Nancy Carolina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Bahia Blanca. Instituto de Invest.bioquimicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; Argentina Fil: Zenklusen, Jean C.. National Institute of Health.The Cancer Genome Atlas Program Office; Estados Unidos Fil: Arevalo, Julian. Hospital Municipal General de Agudos Doctor José Penna; Argentina Fil: Blasco, Jorge. Hospital Municipal General de Agudos Doctor José Penna; Argentina Fil: Lopez, Alejandro. Laboratorios IACA, Bahia Blanca; Argentina Fil: Facchinetti, Maria Marta. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Bahia Blanca. Instituto de Invest.bioquimicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; Argentina Fil: Curino, Alejandro Carlos. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Bahia Blanca. Instituto de Invest.bioquimicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; Argentina |
| Databáze: | OpenAIRE |
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