PMID- 27432152
OWN - NLM
STAT- MEDLINE
DCOM- 20170713
LR  - 20211204
IS  - 1791-2423 (Electronic)
IS  - 1019-6439 (Linking)
VI  - 49
IP  - 4
DP  - 2016 Oct
TI  - L1-CAM knock-down radiosensitizes neuroblastoma IMR-32 cells by simultaneously 
      decreasing MycN, but increasing PTEN protein expression.
PG  - 1722-30
LID - 10.3892/ijo.2016.3625 [doi]
AB  - Childhood neuroblastoma is one of the most malignant types of cancers leading to 
      a high mortality rate. These cancerous cells can be highly metastatic and 
      malignant giving rise to disease recurrence and poor prognosis. The 
      proto-oncogene myelocytomatosis neuroblastoma (MycN) is known to be amplified in 
      this type of cancer, thus, promoting high malignancy and resistance. The L1 cell 
      adhesion molecule (L1-CAM) cleavage has been found upregulated in many types of 
      malignant cancers. In the present study, we explored the interplay between 
      L1-CAM, MycN and PTEN as well as the role played by PDGFR and VEGFR on 
      tumorigenicity in neuroblastoma cells. We investigated the effect of L1-CAM 
      knock-down (KD) and PDGFR/VEGFR inhibition with sunitinib malate (Sutent(R)) 
      treatment on subsequent tumorsphere formation and cellular proliferation and 
      migration in the MycN-amplified IMR-32 neuroblastoma cells. We further examined 
      the effect of combined L1-CAM KD with Sutent treatment or radiotherapy on these 
      cellular functions in our cells. Tumorsphere formation is one of the indicators 
      of aggressiveness in malignant cancers, which was significantly inhibited in 
      IMR-32 cells after L1-CAM KD or Sutent treatment, however, no synergistic effect 
      was observed with dual treatments, rather L1-CAM KD alone showed a greater 
      inhibition on tumorsphere formation compared to Sutent treatment alone. In 
      addition, cellular proliferation and migration were significantly inhibited after 
      L1-CAM KD in the IMR-32 cells with no synergistic effect observed on the rate of 
      cell proliferation when combined with Sutent treatment. Again, L1-CAM KD alone 
      exhibited greater inhibitory effect than Sutent treatment on cell proliferation. 
      L1-CAM KD led to the simultaneous downregulation of MycN, but the upregulation of 
      PTEN protein expression. Notably, radiotherapy (2 Gy) of the IMR-32 cells led to 
      significant upregulation of both L1-CAM and MycN, which was abrogated with L1-CAM 
      KD in our cells. In addition, L1-CAM KD radiosensitized the cells as exhibited by 
      the synergistic effect on the reduction in cell proliferation compared to 
      radiotherapy alone. Taken together, our data show the importance of L1-CAM 
      interplay with MycN and PTEN on the MycN amplified neuroblastoma cell 
      radioresistance, proliferation and motility.
FAU - Rached, Johnny
AU  - Rached J
AD  - Faculty of Sciences, University of Balamand, Koura, Lebanon.
FAU - Nasr, Zeina
AU  - Nasr Z
AD  - Faculty of Sciences, University of Balamand, Koura, Lebanon.
FAU - Abdallah, Jad
AU  - Abdallah J
AD  - School of Pharmacy, Pharmaceutical Sciences Department, Lebanese American 
      University, Byblos, Lebanon.
FAU - Abou-Antoun, Tamara
AU  - Abou-Antoun T
AD  - School of Pharmacy, Pharmaceutical Sciences Department, Lebanese American 
      University, Byblos, Lebanon.
LA  - eng
PT  - Journal Article
DEP - 20160718
PL  - Greece
TA  - Int J Oncol
JT  - International journal of oncology
JID - 9306042
RN  - 0 (MAS1 protein, human)
RN  - 0 (MYCN protein, human)
RN  - 0 (N-Myc Proto-Oncogene Protein)
RN  - 0 (Neural Cell Adhesion Molecule L1)
RN  - 0 (Proto-Oncogene Mas)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.1.3.67 (PTEN protein, human)
SB  - IM
MH  - Blotting, Western
MH  - Cell Movement
MH  - Cell Proliferation
MH  - Gamma Rays
MH  - Gene Expression Regulation, Neoplastic/*radiation effects
MH  - Humans
MH  - N-Myc Proto-Oncogene Protein/*metabolism
MH  - Neural Cell Adhesion Molecule L1/antagonists & inhibitors/*metabolism
MH  - Neuroblastoma/metabolism/pathology/*radiotherapy
MH  - Neuroectodermal Tumors, Primitive, Peripheral/metabolism/pathology/*radiotherapy
MH  - PTEN Phosphohydrolase/*metabolism
MH  - Proto-Oncogene Mas
MH  - *Radiation Tolerance
MH  - Radiotherapy
MH  - Tumor Cells, Cultured
EDAT- 2016/07/20 06:00
MHDA- 2017/07/14 06:00
CRDT- 2016/07/20 06:00
PHST- 2016/04/28 00:00 [received]
PHST- 2016/06/28 00:00 [accepted]
PHST- 2016/07/20 06:00 [entrez]
PHST- 2016/07/20 06:00 [pubmed]
PHST- 2017/07/14 06:00 [medline]
AID - 10.3892/ijo.2016.3625 [doi]
PST - ppublish
SO  - Int J Oncol. 2016 Oct;49(4):1722-30. doi: 10.3892/ijo.2016.3625. Epub 2016 Jul 
      18.