PMID- 21403679
OWN - NLM
STAT- MEDLINE
DCOM- 20120119
LR  - 20211020
IS  - 1748-7838 (Electronic)
IS  - 1001-0602 (Print)
IS  - 1001-0602 (Linking)
VI  - 21
IP  - 10
DP  - 2011 Oct
TI  - Oct-4+/Tenascin C+ neuroblastoma cells serve as progenitors of tumor-derived 
      endothelial cells.
PG  - 1470-86
LID - 10.1038/cr.2011.38 [doi]
AB  - Neuroblastoma (NB)-associated endothelial microvessels (EMs) may be lined by 
      tumor-derived endothelial cells (TECs), that are genetically unstable and 
      chemoresistant. Here we have addressed the identification of TEC progenitors in 
      NB by focusing on Octamer-binding transcription factor 4 (Oct-4) as a putative 
      marker. Oct-4(+) cells were detected in primary NB samples (n = 23), metastatic 
      bone marrow aspirates (n = 10), NB cell lines (n = 4), and orthotopic tumors (n = 
      10) formed by the HTLA-230 NB cell line in immunodeficient mice. Most Oct-4(+) 
      cells showed a perivascular distribution, with 5% of them homing in perinecrotic 
      areas. All Oct-4(+) cells were tumor-derived since they shared amplification of 
      MYCN oncogene with malignant cells. Perivascular Oct-4(+) cells expressed stem 
      cell-related, neural progenitor-related and NB-related markers, including surface 
      Tenascin C (TNC), that was absent from perinecrotic Oct-4(+) cells and bulk tumor 
      cells. TNC(+) but not TNC(-) HTLA-230 cells differentiated in vitro into 
      endothelial-like cells expressing vascular-endothelial-cadherin, 
      prostate-specific membrane antigen and CD31 upon culture in medium containing 
      vascular endothelial growth factor (VEGF). TNC(+) but not TNC(-) HTLA-230 cells 
      formed neurospheres when cultured in serum-free medium. Both cell fractions were 
      tumorigenic, but only tumors formed by TNC(+) cells contained EMs lined by TECs. 
      In conclusion, we have identified in NB tumors two putative niches containing 
      Oct-4(+) tumor cells. Oct-4(+)/TNC(+) perivascular NB cells displayed a high 
      degree of plasticity and served as progenitors of TECs. Therapeutic targeting of 
      Oct4(+)/TNC(+) progenitors may counteract the contribution of NB-derived ECs to 
      tumor relapse and chemoresistance.
FAU - Pezzolo, Annalisa
AU  - Pezzolo A
AD  - Laboratory of Oncology, Istituto Giannina Gaslini, Largo G. Gaslini 5, 16147 
      Genova-Quarto, Italy. annalisapezzolo@ospedale-gaslini.ge.it
FAU - Parodi, Federica
AU  - Parodi F
FAU - Marimpietri, Danilo
AU  - Marimpietri D
FAU - Raffaghello, Lizzia
AU  - Raffaghello L
FAU - Cocco, Claudia
AU  - Cocco C
FAU - Pistorio, Angela
AU  - Pistorio A
FAU - Mosconi, Manuela
AU  - Mosconi M
FAU - Gambini, Claudio
AU  - Gambini C
FAU - Cilli, Michele
AU  - Cilli M
FAU - Deaglio, Silvia
AU  - Deaglio S
FAU - Malavasi, Fabio
AU  - Malavasi F
FAU - Pistoia, Vito
AU  - Pistoia V
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110315
PL  - England
TA  - Cell Res
JT  - Cell research
JID - 9425763
RN  - 0 (MYCN protein, human)
RN  - 0 (N-Myc Proto-Oncogene Protein)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Octamer Transcription Factor-3)
RN  - 0 (Oncogene Proteins)
RN  - 0 (POU5F1 protein, human)
RN  - 0 (Tenascin)
SB  - IM
MH  - Animals
MH  - Bone Marrow/metabolism/pathology
MH  - *Cell Differentiation
MH  - Child
MH  - Child, Preschool
MH  - Drug Resistance, Neoplasm/genetics
MH  - Endothelial Cells/*metabolism/pathology
MH  - Female
MH  - Gene Amplification
MH  - Humans
MH  - Infant
MH  - Male
MH  - Mice
MH  - Mice, Nude
MH  - N-Myc Proto-Oncogene Protein
MH  - Neoplasm Metastasis
MH  - Neoplastic Stem Cells/*metabolism/pathology
MH  - Neovascularization, Pathologic/*metabolism/pathology
MH  - Neuroblastoma/drug therapy/genetics/*metabolism/pathology
MH  - Nuclear Proteins/genetics/metabolism
MH  - Octamer Transcription Factor-3/genetics/*metabolism
MH  - Oncogene Proteins/genetics/metabolism
MH  - Tenascin/genetics/*metabolism
MH  - Transplantation, Heterologous
PMC - PMC3193450
EDAT- 2011/03/16 06:00
MHDA- 2012/01/20 06:00
PMCR- 2012/10/01
CRDT- 2011/03/16 06:00
PHST- 2011/03/16 06:00 [entrez]
PHST- 2011/03/16 06:00 [pubmed]
PHST- 2012/01/20 06:00 [medline]
PHST- 2012/10/01 00:00 [pmc-release]
AID - cr201138 [pii]
AID - 10.1038/cr.2011.38 [doi]
PST - ppublish
SO  - Cell Res. 2011 Oct;21(10):1470-86. doi: 10.1038/cr.2011.38. Epub 2011 Mar 15.