Heme oxygenase (HO)-1 expressing macrophages/microglial cells accumulate during oligodendroglioma progression

Deininger, Martin H.; Meyermann, Richard; Trautmann, Katrin; Duffner, Frank; Grote, E. H.; Wickboldt, Juergen; Schluesener, Hermann J.

doi:10.1016/s0006-8993(00)02594-4

Cited by 59 publications

(39 citation statements)

References 30 publications

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“…To date, only macrophages/microglia present in the stromal compartment of tumors have been shown to express HO-1 [24,25]. In this study, we provide the first report to show that the expression of HO-1 and FoxP3 directly correlate with tumor grade.…”

Section: Discussionmentioning

confidence: 58%

“…Heme oxygenase-1, a key enzyme in heme catabolism, has recently been reported to be expressed by human brain tumors [23], to represent a useful marker for angiogenesis in human gliomas [24], and to accumulate during oligodendroglioma progression [25]. To date, only macrophages/microglia present in the stromal compartment of tumors have been shown to express HO-1 [24,25].…”

Section: Discussionmentioning

confidence: 99%

“…HO-1 expression has also been observed in a wide range of experimental diseases of the rodent brain such as traumatic brain injury [20], ischemia [21], and human Alzheimer's disease [22]. In brain tumors, elevated HO-1 expression has been observed [23,24], and in at least one report, it would appear that HO-1 accumulates during oligodenodroglioma progression [25].…”

Section: Introductionmentioning

confidence: 99%

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CD4+CD25+FoxP3+ T-cell infiltration and heme oxygenase-1 expression correlate with tumor grade in human gliomas

2007

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Regulatory T-cells play an important role in the regulation of the immune response and the mediation of dominant immunologic tolerance. We have previously shown that these cells are elevated in tumors and blood of patients with glioblastoma multiforme. Heme oxygenase-1, a rate-limiting enzyme in heme catabolism, has also been shown to accumulate during glioma progression and to play a critical role in FoxP3 mediated immune suppression. In this study, we investigated the correlation between FoxP3 and HO-1 expression in patients with various grades of astrocytoma (WHO grade II-IV). Using qualitative and quantitative reverse transcriptase-polymerase chain reaction and quantitative flow cytometry analyses, we analyzed FoxP3 and HO-1 expression in 19 patients with different grades of astrocytoma. We observed the highest level of FoxP3 expression in patients with grade IV tumors (11.54 ± 1.95%) vs. grade III (6.74 ± 0.19%) or grade II (2.53 ± 0.11%) (P < 0.05). Moreover, in grade IV tumors, the frequency of HO-1 mRNA expression in CD4 + CD25 + cells was 11.8 ± 2.45% vs. 7.42 ± 0.31% in grade III and 2.33 ± 0.12% in grade II. Tumor infiltrating Treg stained positively with anti-HO-1 antibody. The expression of HO-1 correlated with CD4 + CD25 + FoxP3 + infiltration (r = 0.966). Our results confirm that HO-1 expressing Treg accumulate during glioma progression. This study also suggests that HO-1 mRNA expression is linked to the induction of Foxp3 in CD4 + CD25 + glioma infiltrating Treg. These findings support the suppressive role played by regulatory T-cells in the growth of malignant brain tumors.

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Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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CD4+CD25+FoxP3+ T-cell infiltration and heme oxygenase-1 expression correlate with tumor grade in human gliomas

2007

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“…Elevated expression of HO-1 has also been observed in various tumor cells, including human adenocarcinoma, hepatoma, glioblastoma, melanoma, and squamous carcinoma cells (Goodman et al, 1997;Doi et al, 1999;Tsuki et al, 1999;Deininger et al, 2000;TorisuItakura et al, 2000). Furthermore, increased HO-1 immunoreactive staining is found in benign prostatic hyperplasia and malignant prostate tissue (Maines and Abrahamsson, 1996).…”

Section: Ho-1 and Cell Proliferationmentioning

confidence: 99%

Heme oxygenase‐1 in growth control and its clinical application to vascular disease

Durante

2003

Journal Cellular Physiology

143

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Heme oxygenase-1 (HO-1) catalyzes the degradation of heme to carbon monoxide (CO), iron, and biliverdin. Biliverdin is subsequently metabolized to bilirubin by the enzyme biliverdin reductase. Although interest in HO-1 originally centered on its heme-degrading function, recent findings indicate that HO-1 exerts other biologically important actions. Emerging evidence suggests that HO-1 plays a critical role in growth regulation. Deletion of the HO-1 gene or inhibition of HO-1 activity results in growth retardation and impaired fetal development, whereas HO-1 overexpression increases body size. Although the mechanisms responsible for the growth promoting properties of HO-1 are not well established, HO-1 can indirectly influence growth by regulating the synthesis of growth factors and by modulating the delivery of oxygen or nutrients to specific target tissues. In addition, HO-1 exerts important effects on critical determinants of tissue size, including cell proliferation, apoptosis, and hypertrophy. However, the actions of HO-1 are highly variable and may reflect a role for HO-1 in maintaining tissue homeostasis. Considerable evidence supports a crucial role for HO-1 in blocking the growth of vascular smooth muscle cells (SMCs). This antiproliferative effect of HO-1 is mediated primarily via the release of CO, which inhibits vascular SMC growth via multiple pathways. Pharmacologic or genetic approaches targeting HO-1 or CO to the blood vessel wall may represent a promising, novel therapeutic approach in treating vascular proliferative disorders.

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“…HMOX1 is believed to represent a key enzyme for the protection of cells against 'stress'. Elevated HMOX expression and activity was found in different types of human cancers such as human glioblastoma (14) and pancreatic cancer (15). HMOX1 was also found to accelerate cancer growth and contributes to cellular resistance against chemotherapy and radiotherapy (15,16).…”

Section: Discussionmentioning

confidence: 99%

Differential expression profiling of gene response to ionizing radiation in two endometrial cancer cell lines with distinct radiosensitivities

Jiang²,

Wen³

et al. 2009

Oncol Rep

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Heme oxygenase (HO)-1 expressing macrophages/microglial cells accumulate during oligodendroglioma progression

Cited by 59 publications

References 30 publications

CD4+CD25+FoxP3+ T-cell infiltration and heme oxygenase-1 expression correlate with tumor grade in human gliomas

CD4+CD25+FoxP3+ T-cell infiltration and heme oxygenase-1 expression correlate with tumor grade in human gliomas

Heme oxygenase‐1 in growth control and its clinical application to vascular disease

Differential expression profiling of gene response to ionizing radiation in two endometrial cancer cell lines with distinct radiosensitivities

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