Involvement of Hif-1 in Desferrioxamine-induced Invasion of Glioblastoma Cells

Overview

Journal Clin Exp Metastasis

Specialty Oncology

Date 2007 Mar 16

PMID 17357815

Citations 20

Authors

Anja Elstner

Nikola Holtkamp

Andreas von Deimling

Affiliations

Soon will be listed here.

Abstract

Glioblastoma multiforme are highly invasive brain tumors. Experimental approaches focus on unravelling the mechanisms of invasion, this being a major reason for the poor prognosis of these tumors. Our previous results hinted towards involvement of the iron metabolism in invasion. In this study, we examined the effect of iron depletion on the invasive phenotype of glioblastoma cells. Transwell Matrigel invasion assays were used to monitor iron-dependent invasion of human glioblastoma cell lines U373MG and DBTRG05MG. Intracellular iron concentrations were modulated by applying desferrioxamine (DFO) and ferric ammonium citrate (FAC). We detected enhanced invasion of glioblastoma cells upon DFO-induced iron depletion. Treatment of cells with FAC strongly inhibited invasion. DFO treatment resulted in hypoxia-inducible factor 1 (Hif-1)-mediated induction of urokinase plasminogen activator receptor and matrix metalloproteinase 2. Further, RNA interference-mediated repression of urokinase plasminogen activator receptor inhibited DFO-induced invasion. Our data demonstrate a direct effect of DFO on Hif-1 expression resulting in activation of factors associated with ECM degradation and invasion of glioma cells. These findings caution on utilization of DFO and other iron chelators in the treatment of tumors with invasive potential.

Citing Articles

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Shenoy G, Connor J Neuro Oncol. 2023; 25(12):2136-2149.

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