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Angiogenesis

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01.12.2010 | Original Paper

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

verfasst von: Shoshana Greenberger, Irit Adini, Elisa Boscolo, John B. Mulliken, Joyce Bischoff

Erschienen in: Angiogenesis | Ausgabe 4/2010

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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.

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Titel: Targeting NF-κB in infantile hemangioma-derived stem cells reduces VEGF-A expression
verfasst von: Shoshana Greenberger
Irit Adini
Elisa Boscolo
John B. Mulliken
Joyce Bischoff
Publikationsdatum: 01.12.2010
Verlag: Springer Netherlands
Erschienen in: Angiogenesis / Ausgabe 4/2010
Print ISSN: 0969-6970
Elektronische ISSN: 1573-7209
DOI: https://doi.org/10.1007/s10456-010-9189-6

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

Abstract

Background

Materials and methods

Results

Conclusions

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Background

Materials and methods

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