The level of manganese superoxide dismutase content is an independent prognostic factor for glioblastoma. Biological mechanisms and clinical implications

Ria, Francesco; Landriscina, Matteo; Remiddi, F; Rosselli, Roberto; Iacoangeli, Maurizio; Scerrati, Massimo; Pani, Giovambattista; Borrello, Silvia; Galeotti, T.

doi:10.1054/bjoc.2000.1594

Cited by 43 publications

(30 citation statements)

References 33 publications

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“…Two enzymes involved in nitric oxide generation were selectively expressed in FHA, whereas U87MG cells showed high expression levels of mitochondrial superoxide dismutase (Mn-SOD) and glutathione transferase. Interestingly, Mn-SOD has recently been characterized as an independent prognostic factor for glioblastomas, with high tumor expression levels associated with short median survival (Ria et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Identification of differentially expressed proteins in human glioblastoma cell lines and tumors

Zhang

Tremblay

McDermid

et al. 2003

Glia

112

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KEY WORDSproteomics; matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF); liquid chromatography tandem mass spectrometry (LC-MS-MS); glioblastoma; U87MG; major vault protein; cystatin B; Hsp27; tissue transglutaminase; epidermal growth factor receptor ABSTRACT An in-frame deletion of 801 bp in exons 2-7 (type III mutation) of the epidermal growth factor receptor (EGFR) is detected at high incidence in primary glioblastoma tumors. A proteomic approach was used to generate differential protein expression maps of fetal human astrocytes (FHA), human glioblastoma cell lines U87MG and U87MG expressing type III EGFR deletion (U87MG⌬EGFR) that confers high malignancy to tumor cells. Two-dimensional gel electrophoresis followed by in-gel digestion of separated spots and protein identification by LC-MS-MS and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) identified 23 proteins expressed at higher levels or exclusively in FHA and 29 proteins expressed at higher levels or exclusively in U87MG cells. Three proteins, ubiquitin, cystatin B, and tissue transglutaminase (TTG), were upregulated in U87MG⌬EGFR relative to U87MG. Four proteins highly expressed by U87MG cells, Hsp27, major vault protein, TTG, and cystatin B, were analyzed by Western blot, ELISA, or RT-PCR in cell extracts and in tissue samples of glioblastoma multiforme (GBM; grade IV), low-grade astrocytomas (grades I and II), and nonmalignant brain lesions. All four proteins were highly expressed in GBM tissues compared to nonmalignant brain. These proteins may be used as diagnostic or functional (e.g., multiple drug resistance, invasiveness) markers for glioblastoma tumors. GLIA 42:194 -208, 2003.

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Section: Discussionmentioning

confidence: 99%

Identification of differentially expressed proteins in human glioblastoma cell lines and tumors

Zhang

Tremblay

McDermid

et al. 2003

Glia

112

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“…In recent studies, MnSOD was found to be associated with loss of differentiation and increased clinical malignancy in neuroepithelial origined brain tumors (Landriscina, et al, 1996;Ria, et al, 2001). MnSOD was found significantly positive in Grade IV astrocytomas and medulloblastomas and negative in normal brain samples (Cobbs, et al, 1996).…”

Section: Antioxidant Status Of the Brainmentioning

confidence: 99%

The Stance of Antioxidants in Brain Tumors

Atukeren¹,

Yiğitoğlu²

2013

Clinical Management and Evolving Novel Therapeutic Strategies for Patients With Brain Tumors

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“…MnSOD may also function as a tumor suppressor; for example, it may reduce growth of tumors associated with melanoma (2), pancreatic adenocarcinoma (3,4), colorectal cancer (5), ovarian cancer (6), breast cancer (7), and multiple myeloma (8). Conversely, MnSOD may promote tumor progression in cancers, such as fibrosarcoma (9), gastric cancer (10,11), glioblastoma (12), T-cell lymphoma (13), breast cancer (14,15), cervical cancer (16), prostate cancer (17), and lung cancer (18). Therefore, the precise role of MnSOD in tumorigenesis remains elusive.…”

Section: Introductionmentioning

confidence: 99%

MnSOD Promotes Tumor Invasion via Upregulation of FoxM1–MMP2 Axis and Related with Poor Survival and Relapse in Lung Adenocarcinomas

Chen

Shieh

et al. 2013

Molecular Cancer Research

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Manganese superoxide dismutase (MnSOD) is an antioxidant enzyme responsible for the elimination of superoxide radical. The role of MnSOD in tumor progression in different human cancers is still controversial. In the present study, MnSOD expression in lung cancer cells was explored by knockdown or overexpression using transfection of a short hairpin RNA (shRNA) or an expression vector, respectively, to determine whether MnSOD expression mediates lung cancer cell migration, invasion, and oncogenic potential by increasing FoxM1 and MMP2 expression. Western blotting showed that FoxM1 and MMP2 expression was dependent on MnSOD expression, suggesting that FoxM1 could be upregulated by MnSOD. Three FoxM1 promoters were constructed to verify this activation of FoxM1 by MnSOD and to determine the transcription factors responsible. Luciferase reporter and chromatin immunoprecipitation assays indicated that MnSOD overexpression in lung cancer cells promoted binding of E2F1 and Sp1 to their putative FoxM1 promoter-binding sites and activated FoxM1 reporter activity. MnSOD also enhanced the potential for cell migration, invasion, and anchorage-independent colony growth on soft-agar plates, again via upregulation of FoxM1 and MMP2 expression. In patients with lung cancer, evaluation of MnSOD expression in lung tumors by immunohistochemistry indicated a positive correlation between FoxM1 and MMP2 mRNA expressions. Kaplan-Meier and Cox regression analysis revealed a poorer overall survival (OS) and relapse-free survival (RFS) in patients with MnSOD-positive tumors than with MnSOD-negative tumors. We conclude that MnSOD may promote tumor aggressiveness via upregulation of the FoxM1-MMP2 axis, and that MnSOD expression can independently predict survival and relapse in patients with resected lung adenocarcinoma. Mol Cancer Res; 11(3); 261-71. Ó2012 AACR.

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The level of manganese superoxide dismutase content is an independent prognostic factor for glioblastoma. Biological mechanisms and clinical implications

Cited by 43 publications

References 33 publications

Identification of differentially expressed proteins in human glioblastoma cell lines and tumors

Identification of differentially expressed proteins in human glioblastoma cell lines and tumors

The Stance of Antioxidants in Brain Tumors

MnSOD Promotes Tumor Invasion via Upregulation of FoxM1–MMP2 Axis and Related with Poor Survival and Relapse in Lung Adenocarcinomas

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