Angiogenesis

, Volume 13, Issue 4, pp 327–335 | Cite as

Targeting NF-κB in infantile hemangioma-derived stem cells reduces VEGF-A expression

  • Shoshana Greenberger
  • Irit Adini
  • Elisa Boscolo
  • John B. Mulliken
  • Joyce Bischoff
Original Paper

Abstract

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 κ-light-chain-enhancer of activated B cells (NF-κB). In the present study, we examined the expression of these NF-κB target genes in IH tissue specimens and the effect of NF-κB 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-κB target gene expression by reverse transcription–quantitative PCR (RT-qPCR). The effects of NF-κB 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-κB activity of HemSCs. Velcade (Bortezomib), a proteosome inhibitor that can indirectly inhibit NF-κB, impaired HemSCs viability and expression of pro-angiogenic factors. Furthermore, specific inhibition of NF-κB resulted in suppression of VEGF-A.

Conclusions

We demonstrate expression of NF-κB 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.

Keywords

Hemangioma-derived stem cells Infantile hemangioma Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) Urokinase plasminogen activator receptor (uPAR) VEGF 

Supplementary material

10456_2010_9189_MOESM1_ESM.docx (223 kb)
Supplementary material 1 (DOCX 222 kb)

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Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Shoshana Greenberger
    • 1
  • Irit Adini
    • 1
  • Elisa Boscolo
    • 1
  • John B. Mulliken
    • 2
  • Joyce Bischoff
    • 1
  1. 1.Vascular Biology Program and Department of SurgeryChildren’s Hospital Boston and Harvard Medical SchoolBostonUSA
  2. 2.Department of Plastic SurgeryChildren’s Hospital Boston and Harvard Medical SchoolBostonUSA

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