Nuclear localization of heme oxygenase-1 is associated with tumor progression of head and neck squamous cell carcinomas
| Autor: | J. Silvio Gutkind, Vyomesh Patel, Maria Marta Facchinetti, Norberto Ariel Gandini, Alejandro Carlos Curino, Débora Gisele Salomón, Jorge Alejandro Blasco, María Eugenia Fermento, Alfredo A. Molinolo |
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| Rok vydání: | 2011 |
| Předmět: |
Male
Pathology medicine.medical_specialty Clinical Biochemistry Cell Biology Polymerase Chain Reaction Pathology and Forensic Medicine Mice medicine Animals Humans RNA Messenger Molecular Biology Aged Tissue microarray Paraffin Embedding Head and neck cancer Middle Aged medicine.disease Prognosis Head and neck squamous-cell carcinoma Heme oxygenase stomatognathic diseases Disease Models Animal medicine.anatomical_structure Tumor progression Cell culture Head and Neck Neoplasms Tissue Array Analysis Carcinoma Squamous Cell Disease Progression Immunohistochemistry Female Heme Oxygenase-1 |
| Zdroj: | Experimental and molecular pathology. 93(2) |
| ISSN: | 1096-0945 |
| Popis: | The expression of heme oxygenase-1 (HO-1) was shown to be increased in multiple tumors compared with their surrounding healthy tissues and was also observed to be up-regulated in oral squamous cell carcinomas (OSCC). However, conflicting results were obtained and little information is available regarding HO-1 significance in head and neck squamous cell carcinoma (HNSCC). Therefore, the aim of the present study was to perform a wide screening of HO-1 expression in a large collection of human primary HNSCCs and to correlate the results with clinical and pathological parameters. For this purpose, we investigated the expression of this protein by immunohistochemistry (IHC) in tissue microarrays (TMAs) of HNSCC and in an independent cohort of paraffin-embedded tumor specimens. HO-1 expression was further validated by real-time qPCR performed on selected laser capture-microdissected (LCM) oral tissue samples. Both the number of HO-1-positive samples and HO-1 immunoreactivity in the cancerous tissues were significantly higher than those in the non-tumor tissues. These results were confirmed at the mRNA level. Interestingly, HO-1 localization was observed in the nucleus, and the rate of nuclear HO-1 in HNSCC was higher than that in non-malignant tissues. Nuclear HO-1 was observed in HNSCC cell lines and increased even further following hemin treatment. Analysis of HO-1 expression and sub-cellular localization in a mouse model of squamous cell carcinoma (SCC) and in human HNSCC revealed that nuclear HO-1 increases with tumor progression. Taken together, these results demonstrate that HO-1 is up-regulated in HNSCC and that nuclear localization of HO-1 is associated with malignant progression in this tumor type. |
| Databáze: | OpenAIRE |
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