PMID- 20872175
OWN - NLM
STAT- MEDLINE
DCOM- 20110217
LR  - 20211020
IS  - 1573-7209 (Electronic)
IS  - 0969-6970 (Print)
IS  - 0969-6970 (Linking)
VI  - 13
IP  - 4
DP  - 2010 Dec
TI  - Targeting NF-kappaB in infantile hemangioma-derived stem cells reduces VEGF-A 
      expression.
PG  - 327-35
LID - 10.1007/s10456-010-9189-6 [doi]
AB  - BACKGROUND: infantile hemangioma (IH) is a most common tumor of infancy. Using 
      infantile hemangioma-derived stem cells (HemSCs), we recently demonstrated that 
      corticosteroids suppress the expression of VEGF-A, monocyte chemoattractant 
      protein-1 (MCP-1), urokinase plasminogen activator receptor (uPAR), and 
      interleukin-6 (IL-6); each of these are known targets of the transcription factor 
      nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB). In the 
      present study, we examined the expression of these NF-kappaB target genes in IH 
      tissue specimens and the effect of NF-kappaB regulation on the expression of 
      pro-angiogenic cytokines, and in particular VEGF-A, in HemSCs. MATERIALS AND 
      METHODS: RNA extracted from IH tissue and hemangioma-derived stem cells (HemSCs) 
      was used to analyze NF-kappaB target gene expression by reverse 
      transcription-quantitative PCR (RT-qPCR). The effects of NF-kappaB blockade were 
      examined in HemSCs. Immunostaining, immunoblotting and ELISA were used to assess 
      protein expression. RESULTS: MCP-1, uPAR, and IL-6 were found to be 
      differentially expressed in proliferating versus involuting IH. Corticosteroids 
      suppressed NF-kappaB activity of HemSCs. Velcade (Bortezomib), a proteosome inhibitor 
      that can indirectly inhibit NF-kappaB, impaired HemSCs viability and expression of 
      pro-angiogenic factors. Furthermore, specific inhibition of NF-kappaB resulted in 
      suppression of VEGF-A. CONCLUSIONS: we demonstrate expression of NF-kappaB target 
      genes in proliferating IH. In addition, we show that the expression of several 
      pro-angiogenic factors in HemSCs, and in particular VEGF-A, is regulated by NF-B 
      activity.
FAU - Greenberger, Shoshana
AU  - Greenberger S
AD  - Department of Surgery, Children's Hospital Boston and Harvard Medical School, 
      Boston, MA 02115, USA.
FAU - Adini, Irit
AU  - Adini I
FAU - Boscolo, Elisa
AU  - Boscolo E
FAU - Mulliken, John B
AU  - Mulliken JB
FAU - Bischoff, Joyce
AU  - Bischoff J
LA  - eng
GR  - R01 HL096384/HL/NHLBI NIH HHS/United States
GR  - R01 HL096384-03/HL/NHLBI NIH HHS/United States
PT  - Evaluation Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100925
PL  - Germany
TA  - Angiogenesis
JT  - Angiogenesis
JID - 9814575
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Boronic Acids)
RN  - 0 (NF-kappa B)
RN  - 0 (Pyrazines)
RN  - 0 (VEGFA protein, human)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 69G8BD63PP (Bortezomib)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - Hemangioma, capillary infantile
SB  - IM
MH  - Antineoplastic Agents/pharmacology/*therapeutic use
MH  - Boronic Acids/pharmacology
MH  - Bortezomib
MH  - Cell Proliferation/drug effects
MH  - Child
MH  - Child, Preschool
MH  - Dexamethasone/pharmacology
MH  - Female
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Hemangioma, Capillary/congenital/drug therapy/genetics/metabolism/pathology
MH  - Humans
MH  - Infant
MH  - Infant, Newborn
MH  - Male
MH  - Molecular Targeted Therapy/methods
MH  - NF-kappa B/*antagonists & inhibitors/genetics/metabolism
MH  - Neoplastic Stem Cells/drug effects/*metabolism/pathology
MH  - Neoplastic Syndromes, Hereditary
MH  - Pyrazines/pharmacology
MH  - Skin Neoplasms/*drug therapy/genetics/metabolism/pathology
MH  - Vascular Endothelial Growth Factor A/*genetics/metabolism
PMC - PMC3034388
MID - NIHMS268304
COIS- The authors have declared that no conflict of interest exists.
EDAT- 2010/09/28 06:00
MHDA- 2011/02/18 06:00
PMCR- 2011/12/01
CRDT- 2010/09/28 06:00
PHST- 2010/06/11 00:00 [received]
PHST- 2010/09/09 00:00 [accepted]
PHST- 2010/09/28 06:00 [entrez]
PHST- 2010/09/28 06:00 [pubmed]
PHST- 2011/02/18 06:00 [medline]
PHST- 2011/12/01 00:00 [pmc-release]
AID - 10.1007/s10456-010-9189-6 [doi]
PST - ppublish
SO  - Angiogenesis. 2010 Dec;13(4):327-35. doi: 10.1007/s10456-010-9189-6. Epub 2010 
      Sep 25.