PMID- 24608791
OWN - NLM
STAT- MEDLINE
DCOM- 20150901
LR  - 20220514
IS  - 1476-5403 (Electronic)
IS  - 1350-9047 (Print)
IS  - 1350-9047 (Linking)
VI  - 21
IP  - 7
DP  - 2014 Jul
TI  - Conversion of differentiated cancer cells into cancer stem-like cells in a 
      glioblastoma model after primary chemotherapy.
PG  - 1119-31
LID - 10.1038/cdd.2014.31 [doi]
AB  - Glioblastoma multiforme patients have a poor prognosis due to therapeutic 
      resistance and tumor relapse. It has been suggested that gliomas are driven by a 
      rare subset of tumor cells known as glioma stem cells (GSCs). This hypothesis 
      states that only a few GSCs are able to divide, differentiate, and initiate a new 
      tumor. It has also been shown that this subpopulation is more resistant to 
      conventional therapies than its differentiated counterpart. In order to 
      understand glioma recurrence post therapy, we investigated the behavior of GSCs 
      after primary chemotherapy. We first show that exposure of patient-derived as 
      well as established glioma cell lines to therapeutic doses of temozolomide (TMZ), 
      the most commonly used antiglioma chemotherapy, consistently increases the GSC 
      pool over time both in vitro and in vivo. Secondly, lineage-tracing analysis of 
      the expanded GSC pool suggests that such amplification is a result of a 
      phenotypic shift in the non-GSC population to a GSC-like state in the presence of 
      TMZ. The newly converted GSC population expresses markers associated with 
      pluripotency and stemness, such as CD133, SOX2, Oct4, and Nestin. Furthermore, we 
      show that intracranial implantation of the newly converted GSCs in nude mice 
      results in a more efficient grafting and invasive phenotype. Taken together, 
      these findings provide the first evidence that glioma cells exposed to 
      chemotherapeutic agents are able to interconvert between non-GSCs and GSCs, 
      thereby replenishing the original tumor population, leading to a more 
      infiltrative phenotype and enhanced chemoresistance. This may represent a 
      potential mechanism for therapeutic relapse.
FAU - Auffinger, B
AU  - Auffinger B
AD  - The Brain Tumor Center, The University of Chicago, Chicago, IL, USA.
FAU - Tobias, A L
AU  - Tobias AL
AD  - The Brain Tumor Center, The University of Chicago, Chicago, IL, USA.
FAU - Han, Y
AU  - Han Y
AD  - The Brain Tumor Center, The University of Chicago, Chicago, IL, USA.
FAU - Lee, G
AU  - Lee G
AD  - The Brain Tumor Center, The University of Chicago, Chicago, IL, USA.
FAU - Guo, D
AU  - Guo D
AD  - The Brain Tumor Center, The University of Chicago, Chicago, IL, USA.
FAU - Dey, M
AU  - Dey M
AD  - The Brain Tumor Center, The University of Chicago, Chicago, IL, USA.
FAU - Lesniak, M S
AU  - Lesniak MS
AD  - 1] The Brain Tumor Center, The University of Chicago, Chicago, IL, USA [2] 
      Department of Surgery, The University of Chicago, Chicago, IL, USA.
FAU - Ahmed, A U
AU  - Ahmed AU
AD  - 1] The Brain Tumor Center, The University of Chicago, Chicago, IL, USA [2] 
      Department of Surgery, The University of Chicago, Chicago, IL, USA.
LA  - eng
GR  - K99 CA160775/CA/NCI NIH HHS/United States
GR  - U01 NS069997/NS/NINDS NIH HHS/United States
GR  - R00 CA160775/CA/NCI NIH HHS/United States
GR  - R01 CA138587/CA/NCI NIH HHS/United States
GR  - R00CA160775/CA/NCI NIH HHS/United States
GR  - R01CA138587/CA/NCI NIH HHS/United States
GR  - K99CA160775/CA/NCI NIH HHS/United States
GR  - R01 CA122930/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140307
PL  - England
TA  - Cell Death Differ
JT  - Cell death and differentiation
JID - 9437445
RN  - 0 (Antineoplastic Agents, Alkylating)
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 1B37H0967P (endothelial PAS domain-containing protein 1)
RN  - 7GR28W0FJI (Dacarbazine)
RN  - YF1K15M17Y (Temozolomide)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents, Alkylating/*pharmacology/therapeutic use
MH  - Basic Helix-Loop-Helix Transcription Factors/metabolism
MH  - Brain Neoplasms/drug therapy/*pathology
MH  - Cell Line, Tumor
MH  - Cell Transformation, Neoplastic/*drug effects
MH  - Dacarbazine/*analogs & derivatives/pharmacology/therapeutic use
MH  - Glioblastoma/drug therapy/*pathology
MH  - Humans
MH  - Male
MH  - Mice, Nude
MH  - Neoplastic Stem Cells/*physiology
MH  - Phenotype
MH  - Temozolomide
MH  - Xenograft Model Antitumor Assays
PMC - PMC4207480
EDAT- 2014/03/13 06:00
MHDA- 2015/09/02 06:00
PMCR- 2015/07/01
CRDT- 2014/03/11 06:00
PHST- 2013/08/11 00:00 [received]
PHST- 2014/02/03 00:00 [revised]
PHST- 2014/02/03 00:00 [accepted]
PHST- 2014/03/11 06:00 [entrez]
PHST- 2014/03/13 06:00 [pubmed]
PHST- 2015/09/02 06:00 [medline]
PHST- 2015/07/01 00:00 [pmc-release]
AID - cdd201431 [pii]
AID - 10.1038/cdd.2014.31 [doi]
PST - ppublish
SO  - Cell Death Differ. 2014 Jul;21(7):1119-31. doi: 10.1038/cdd.2014.31. Epub 2014 
      Mar 7.