Involvement of Hif-1 in desferrioxamine-induced invasion of glioblastoma cells

Elstner, Anja; Holtkamp, Nikola; Deimling, Andreas von

doi:10.1007/s10585-007-9057-y

Cited by 41 publications

(27 citation statements)

References 38 publications

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“…23 MMP-2 transcription is up-regulated during HIF-1α stabilization, which does not increase MMP-9 levels; similar to what we saw in our study. 24, 25 Moreover, multiple downstream targets of HIF-1α are up-regulated during anti-angiogenic therapy. 18 Based on these data, we evaluated HIF-1α expression in U251 glioma cells and found it to be up-regulated as early as 8 hours post therapy (Supplementary Figure S1).…”

Section: Discussionmentioning

confidence: 99%

Anti-angiogenic therapy increases intratumoral adenovirus distribution by inducing collagen degradation

et al. 2012

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Conditionally replicating adenoviruses (CRAd) are a promising class of gene therapy agents that can overcome already known glioblastoma (GBM) resistance mechanisms but have limited distribution upon direct intratumoral (i.t.) injection. Collagen bundles in the extracellular matrix (ECM) play an important role in inhibiting virus distribution. In fact, ECM pre-treatment with collagenases improves virus distributions to tumor cells. Matrix metalloproteinases (MMPs) are an endogenous class of collagenases secreted by tumor cells whose function can be altered by different drugs including anti-angiogenic agents, such as bevacizumab. In this study we hypothesized that up-regulation of MMP activity during antiangiogenic therapy can improve CRAd-S-pk7 distribution in GBM. We find that MMP-2 activity in human U251 GBM xenografts increases (*p=0.03) and collagen IV content decreases (*p=0.01) during vascular endothelial growth factor (VEGF-A) antibody neutralization. After proving that collagen IV inhibits CRAd-S-pk7 distribution in U251 xenografts (Spearman rho= −0.38; **p=0.003), we show that VEGF blocking antibody treatment followed by CRAd-S-pk7 i.t. injection reduces U251 tumor growth more than each individual agent alone (***p<0.0001). Our data proposes a novel approach to improve virus distribution in tumors by relying on the early effects of anti-angiogenic therapy.

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Section: Discussionmentioning

confidence: 99%

Anti-angiogenic therapy increases intratumoral adenovirus distribution by inducing collagen degradation

et al. 2012

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“…Pseudopalisades around necrotic foci, a common feature of high-grade gliomas, are severely hypoxic and linked to waves of glioma cells actively migrating away from such oxygen-deficient regions [83][84][85]87]. Experimental studies further suggest that tumour hypoxia results in increased glioma cell migration and invasion, and strongly correlates with tumour malignancy [39,88,89]. The exact pathophysiological factors and mechanisms underlying hypoxia-induced cell migration in gliomas are still not known, and further investigation is required to understand the complex molecular pathways involved in hypoxic responses and metabolic control by glioma cells.…”

Section: Hypoxia-induced Migrationmentioning

confidence: 99%

The biology and mathematical modelling of glioma invasion: a review

Alfonso

Talkenberger

Seifert

et al. 2017

J. R. Soc. Interface.

183

163

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Adult gliomas are aggressive brain tumours associated with low patient survival rates and limited life expectancy. The most important hallmark of this type of tumour is its invasive behaviour, characterized by a markedly phenotypic plasticity, infiltrative tumour morphologies and the ability of malignant progression from low-to high-grade tumour types. Indeed, the widespread infiltration of healthy brain tissue by glioma cells is largely responsible for poor prognosis and the difficulty of finding curative therapies. Meanwhile, mathematical models have been established to analyse potential mechanisms of glioma invasion. In this review, we start with a brief introduction to current biological knowledge about glioma invasion, and then critically review and highlight future challenges for mathematical models of glioma invasion.

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“…In fact, the effect of iron depletion on activation of HIF-1␣ has been linked to the stimulation of tumor angiogenesis and resistance to chemotherapy. For example, Elstner et al, (2007) showed that DFO-induced iron depletion significantly enhanced glioblastoma cell invasion in vitro. However, apart from its tumor-stimulating activity, HIF-1␣ can also potentially have antitumor effects by up-regulating the pro-apoptotic molecule BNIP3 (Bruick, 2000) and the potent tumor suppressor p53 (An et al, 1998).…”

Section: Identification Of Novel Iron-regulated Molecules 453mentioning

confidence: 99%

Iron Chelator-Mediated Alterations in Gene Expression: Identification of Novel Iron-Regulated Molecules That Are Molecular Targets of Hypoxia-Inducible Factor-1α and p53

Saletta

Rahmanto²,

Noulsri

et al. 2009

Mol Pharmacol

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Iron deficiency affects 500 million people, yet the molecular role of iron in gene expression remains poorly characterized. In addition, the alterations in global gene expression after iron chelation remain unclear and are important to assess for understanding the molecular pathology of iron deficiency and the biological effects of chelators. Considering this, we assessed the effect on whole genome gene expression of two iron chelators (desferrioxamine and 2-hydroxy-1-napthylaldehyde isonicotinoyl hydrazone) that have markedly different permeability properties. Sixteen genes were significantly regulated by both ligands, whereas a further 50 genes were significantly regulated by either compound. Apart from ironmediated regulation of expression via hypoxia inducible factor-1␣, it was noteworthy that the transcription factor p53 was also involved in iron-regulated gene expression. Examining 16 genes regulated by both chelators in normal and neoplastic cells, five genes (APP, GDF15, CITED2, EGR1, and PNRC1) were significantly differentially expressed between the cell types. In view of their functions in tumor suppression, proliferation, and apoptosis, these findings are important for understanding the selective antiproliferative effects of chelators against neoplastic cells. Most of the genes identified have not been described previously to be iron-regulated and are important for understanding the molecular and cellular effects of iron depletion.Iron deficiency affects approximately 500 million people. However, despite the enormity of this problem, very little is understood concerning the precise molecular roles played by iron in growth, cell-cycle progression, and apoptosis.Iron plays essential roles in cells, including DNA synthesis and cell cycle control (Buss et al., 2003). It is well known that iron deficiency induced by chelators results in a G 1 /S arrest and apoptosis (Buss et al., 2003). The best-characterized role of iron in proliferation involves its function in the rate-limiting step of DNA synthesis catalyzed by ribonucleotide reductase (Buss et al., 2003). Iron has also been shown to regulate the expression of a variety of molecules involved in cell-cycle control (e.g., p21CIP1/WAF1 , GADD45, p53, cyclin D1, etc.) (Gao and Richardson, 2001;Liang and Richardson, 2003) and metastasis suppression (e.g., N-myc downstreamregulated gene-1; NDRG-1) (Le and Richardson, 2004). Because iron is important for mitochondrial heme and iron sulfur cluster synthesis, it is likely that iron chelation will also affect basic mitochondrial metabolism and function.Iron chelators are well known therapeutics for the treatment of iron-overload disease and some of these agents show potential for cancer therapy (Buss et al., 2003;Whitnall et al., 2006 ABBREVIATIONS: 311, 2-hydroxy-1-napthylaldehyde isonicotinoyl hydrazone; DFO, desferrioxamine; IRP, iron-regulatory protein; IRE, ironresponsive element; UTR, untranslated region; HIF-1, hypoxia-inducible factor-1; HUVEC, human umbilical vein endothelial cell; MEF, murine e...

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Involvement of Hif-1 in desferrioxamine-induced invasion of glioblastoma cells

Cited by 41 publications

References 38 publications

Anti-angiogenic therapy increases intratumoral adenovirus distribution by inducing collagen degradation

Anti-angiogenic therapy increases intratumoral adenovirus distribution by inducing collagen degradation

The biology and mathematical modelling of glioma invasion: a review

Iron Chelator-Mediated Alterations in Gene Expression: Identification of Novel Iron-Regulated Molecules That Are Molecular Targets of Hypoxia-Inducible Factor-1α and p53

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