PMID- 23947765
OWN - NLM
STAT- MEDLINE
DCOM- 20140325
LR  - 20220520
IS  - 1476-4598 (Electronic)
IS  - 1476-4598 (Linking)
VI  - 12
IP  - 1
DP  - 2013 Aug 16
TI  - Non-small cell lung cancer cells survived ionizing radiation treatment display 
      cancer stem cell and epithelial-mesenchymal transition phenotypes.
PG  - 94
LID - 10.1186/1476-4598-12-94 [doi]
AB  - Ionizing radiation (IR) is used for patients diagnosed with unresectable non 
      small cell lung cancer (NSCLC), however radiotherapy remains largely palliative 
      due to radioresistance. Cancer stem cells (CSCs), as well as 
      epithelial-mesenchymal transition (EMT), may contribute to drug and radiation 
      resistance mechanisms in solid tumors. Here we investigated the molecular 
      phenotype of A549 and H460 NSCLC cells that survived treatment with IR (5Gy) and 
      are growing as floating tumor spheres and cells that are maintained in a 
      monolayer after irradiation.Non-irradiated and irradiated cells were collected 
      after one week, seeded onto ultra low attachment plates and propagated as tumor 
      spheres. Bulk NSCLC cells which survived radiation and grew in spheres express 
      cancer stem cell surface and embryonic stem cell markers and are able to 
      self-renew, and generate differentiated progeny. These cells also have a 
      mesenchymal phenotype. Particularly, the radiation survived sphere cells express 
      significantly higher levels of CSC markers (CD24 and CD44), nuclear beta-catenin and 
      EMT markers (Snail1, Vimentin, and N-cadherin) than non-irradiated lung tumor 
      sphere cells. Upregulated levels of Oct-4, Sox2 and beta-catenin were detected in 
      H460 cells maintained in a monolayer after irradiation, but not in radiation 
      survived adherent A459 cells.PDGFR-beta was upregulated in radiation survived 
      sphere cells and in radiation survived adherent cells in both A549 and H460 cell 
      lines. Combining IR treatment with axitinib or dasatinib, inhibitors with 
      anti-PDFGR activity, potentiates the efficacy of NSCLC radiotherapy in vitro.Our 
      findings suggest that radiation survived cells have a complex phenotype combining 
      the properties of CSCs and EMT. CD44, SNAIL and PDGFR-beta are dramatically 
      upregulated in radiation survived cells and might be considered as markers of 
      radiotherapy response in NSCLC.
FAU - Gomez-Casal, Roberto
AU  - Gomez-Casal R
AD  - University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA.
FAU - Bhattacharya, Chitralekha
AU  - Bhattacharya C
FAU - Ganesh, Nandita
AU  - Ganesh N
FAU - Bailey, Lisa
AU  - Bailey L
FAU - Basse, Per
AU  - Basse P
FAU - Gibson, Michael
AU  - Gibson M
FAU - Epperly, Michael
AU  - Epperly M
FAU - Levina, Vera
AU  - Levina V
LA  - eng
GR  - 1R21CA164740-01/CA/NCI NIH HHS/United States
GR  - P30CA047904/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 - 20130816
PL  - England
TA  - Mol Cancer
JT  - Molecular cancer
JID - 101147698
RN  - 0 (CD44 protein, human)
RN  - 0 (Hyaluronan Receptors)
RN  - 0 (SNAI1 protein, human)
RN  - 0 (Snail Family Transcription Factors)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor beta)
SB  - IM
MH  - Carcinoma, Non-Small-Cell Lung/*pathology/radiotherapy
MH  - Cell Line, Tumor
MH  - Epithelial-Mesenchymal Transition/*radiation effects
MH  - Humans
MH  - Hyaluronan Receptors/genetics/metabolism
MH  - Lung Neoplasms/*pathology/radiotherapy
MH  - Neoplastic Stem Cells/metabolism/pathology/*radiation effects
MH  - *Phenotype
MH  - Radiation Tolerance
MH  - Receptor, Platelet-Derived Growth Factor beta/genetics/metabolism
MH  - Snail Family Transcription Factors
MH  - Transcription Factors/genetics/metabolism
MH  - Up-Regulation
PMC - PMC3751356
EDAT- 2013/08/21 06:00
MHDA- 2014/03/26 06:00
PMCR- 2013/08/16
CRDT- 2013/08/17 06:00
PHST- 2013/04/03 00:00 [received]
PHST- 2013/08/14 00:00 [accepted]
PHST- 2013/08/17 06:00 [entrez]
PHST- 2013/08/21 06:00 [pubmed]
PHST- 2014/03/26 06:00 [medline]
PHST- 2013/08/16 00:00 [pmc-release]
AID - 1476-4598-12-94 [pii]
AID - 10.1186/1476-4598-12-94 [doi]
PST - epublish
SO  - Mol Cancer. 2013 Aug 16;12(1):94. doi: 10.1186/1476-4598-12-94.