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Description
  • Tumor-initiating cells (TICs) often survive therapy and give rise to second-line tumors. We tested the plausibility of sphere cultures as models of TICs. Microarray data and microRNA data analysis confirmed the validity of spheres as models of TICs for breast and prostate cancer as well as mesothelioma cell lines. Microarray data analysis revealed the Trp pathway as the only pathway upregulated significantly in all types of studied TICs, with increased levels of indoleamine-2,3-dioxygenase-1 (IDO1), the rate-limiting enzyme of Trp metabolism along the kynurenine pathway. All types of TICs also expressed higher levels of the Trp uptake system consisting of CD98 and LAT1 with functional consequences. IDO1 expression was regulated via both transcriptional and posttranscriptional mechanisms, depending on the cancer type. Serial transplantation of TICs in mice resulted in gradually increased IDO1. Mitocans, represented by et-tocopheryl succinate and mitochondrially targeted vitamin E succinate (MitoVES), suppressed IDO1 in TICs. MitoVES suppressed IDO1 in TICs with functional mitochondrial complex II, involving transcriptional and posttranscriptional mechanisms. IDO1 increase and its suppression by VE analogues were replicated in TICs from primary human glioblastomas. Our work indicates that IDO1 is increased in TICs and that mitocans suppress the protein. (C) 2013 Elsevier Inc. All rights reserved.
  • Tumor-initiating cells (TICs) often survive therapy and give rise to second-line tumors. We tested the plausibility of sphere cultures as models of TICs. Microarray data and microRNA data analysis confirmed the validity of spheres as models of TICs for breast and prostate cancer as well as mesothelioma cell lines. Microarray data analysis revealed the Trp pathway as the only pathway upregulated significantly in all types of studied TICs, with increased levels of indoleamine-2,3-dioxygenase-1 (IDO1), the rate-limiting enzyme of Trp metabolism along the kynurenine pathway. All types of TICs also expressed higher levels of the Trp uptake system consisting of CD98 and LAT1 with functional consequences. IDO1 expression was regulated via both transcriptional and posttranscriptional mechanisms, depending on the cancer type. Serial transplantation of TICs in mice resulted in gradually increased IDO1. Mitocans, represented by et-tocopheryl succinate and mitochondrially targeted vitamin E succinate (MitoVES), suppressed IDO1 in TICs. MitoVES suppressed IDO1 in TICs with functional mitochondrial complex II, involving transcriptional and posttranscriptional mechanisms. IDO1 increase and its suppression by VE analogues were replicated in TICs from primary human glioblastomas. Our work indicates that IDO1 is increased in TICs and that mitocans suppress the protein. (C) 2013 Elsevier Inc. All rights reserved. (en)
Title
  • Indoleamine-2,3-dioxygenase elevated in tumor-initiating cells is suppressed by mitocans
  • Indoleamine-2,3-dioxygenase elevated in tumor-initiating cells is suppressed by mitocans (en)
skos:prefLabel
  • Indoleamine-2,3-dioxygenase elevated in tumor-initiating cells is suppressed by mitocans
  • Indoleamine-2,3-dioxygenase elevated in tumor-initiating cells is suppressed by mitocans (en)
skos:notation
  • RIV/00216208:11310/14:10271592!RIV15-MSM-11310___
http://linked.open...avai/riv/aktivita
http://linked.open...avai/riv/aktivity
  • I, P(GAP301/10/1937), P(GAP305/12/1708), S
http://linked.open...iv/cisloPeriodika
  • neuveden
http://linked.open...vai/riv/dodaniDat
http://linked.open...aciTvurceVysledku
http://linked.open.../riv/druhVysledku
http://linked.open...iv/duvernostUdaju
http://linked.open...titaPredkladatele
http://linked.open...dnocenehoVysledku
  • 21220
http://linked.open...ai/riv/idVysledku
  • RIV/00216208:11310/14:10271592
http://linked.open...riv/jazykVysledku
http://linked.open.../riv/klicovaSlova
  • Free radicals; Mitochondrially targeted vitamin E succinate; Mitocans; Tumor-initiating cells; IDO (en)
http://linked.open.../riv/klicoveSlovo
http://linked.open...odStatuVydavatele
  • US - Spojené státy americké
http://linked.open...ontrolniKodProRIV
  • [7DEF3650681A]
http://linked.open...i/riv/nazevZdroje
  • Free Radical Biology and Medicine
http://linked.open...in/vavai/riv/obor
http://linked.open...ichTvurcuVysledku
http://linked.open...cetTvurcuVysledku
http://linked.open...vavai/riv/projekt
http://linked.open...UplatneniVysledku
http://linked.open...v/svazekPeriodika
  • 67
http://linked.open...iv/tvurceVysledku
  • Neužil, Jiří
  • Prokopová, Kateřina
  • Truksa, Jaroslav
  • Dong, Lan-Feng
  • Ralph, Stephen J.
  • Ansorge, Olaf
  • Bajzikova, Martina
  • Goodwin, Jacob
  • Grant, Gary
  • Hall, Susan
  • Meedeniya, Adrian C. B.
  • Nguyen, Maria Nga
  • Pasdar, Elham Alizadeh
  • Stantic, Marina
  • Stapelberg, Michael
  • Stursa, Jan
  • Thai, Thuan
  • Thomas, Shane R.
  • Walker, Tom
  • Yan, Bing
  • Zobalova, Renata
  • de Pennington, Nicholas
http://linked.open...ain/vavai/riv/wos
  • 000331854200005
issn
  • 0891-5849
number of pages
http://bibframe.org/vocab/doi
  • 10.1016/j.freeradbiomed.2013.10.003
http://localhost/t...ganizacniJednotka
  • 11310
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