Synergistic Effect of TNF-α in Soluble VCAM-1-Induced Angiogenesis Through α4 Integrins

Nakao, Shintaro; Kuwano, Takashi; Ishibashi, Tatsuro; Kuwano, Michihiko; Ono, Masahiro

doi:10.4049/jimmunol.170.11.5704

Cited by 76 publications

(73 citation statements)

References 48 publications

(46 reference statements)

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“…Antigen-antibody complexes were then visualized with horseradish peroxidase-conjugated secondary antibodies following by enhanced chemiluminescence (ECL; Amersham, Piscataway, NJ), as described previously. 14,29) Corneal micropocket assay in mice and quantification of corneal neo-vascularization. The corneal micropocket assay was performed essentially as previously described.…”

Section: Methodsmentioning

confidence: 99%

Direct inhibition of EGF receptor activation in vascular endothelial cells by gefitinib (‘Iressa’, ZD1839)

et al. 2004

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Section: Methodsmentioning

confidence: 99%

Direct inhibition of EGF receptor activation in vascular endothelial cells by gefitinib (‘Iressa’, ZD1839)

et al. 2004

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“…5A). The activation of the ERK1/2 signaling pathway presumably plays a pivotal role in the stimulation of endothelial cell proliferation (41,54). However, it also protects cells from many forms of apoptosis (55,56).…”

Section: Pharmacoproteomic Analysis Of P11mentioning

confidence: 99%

Pharmacoproteomic Analysis of a Novel Cell-permeable Peptide Inhibitor of Tumor-induced Angiogenesis

Bang

Kim

Kang

et al. 2011

Molecular & Cellular Proteomics

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P11, a novel peptide ligand containing a PDZ-binding motif (Ser-Asp-Val) with high affinity to integrin ␣ v ␤ 3 was identified from a hexapeptide library (PS-SPCL) using a protein microarray chip-based screening system. Here, we investigated the inhibitory mechanism of P11 (HSD-VHK) on tumor-induced angiogenesis via a pharmacoproteomic approach. P11 was rapidly internalized by , human umbilical vein endothelial cells (HUVECs) via an integrin ␣ v ␤ 3 -mediated event. Caveolin and clathrin appeared to be involved in the P11 uptake process. The cell-penetrating P11 resulted in suppression of bFGF-induced HUVEC proliferation in a dose-dependent manner. Phosphorylation of extracellular-signal regulated kinase (ERK1/2) and mitogen-activated protein kinase kinase (MEK) in bFGFstimulated HUVECs was inhibited by cell-permeable P11. Proteomic analysis via antibody microarray showed upregulation of p53 in P11-treated HUVECs, resulting in induction of apoptosis via activation of caspases-3, -8, and -9. Several lines of experimental evidence strongly suggest that the molecular mechanism of P11, a novel antiangiogenic agent, inhibits bFGF-induced HUVEC proliferation via mitogen-activated protein kinase kinase and extracellular-signal regulated kinase inhibition as well as p53-mediated apoptosis related with activation of

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“…Integrins are a family of transmembrane receptors known to play roles in adhesion and migration (Watt, 2002). TNF-a has recently been shown to regulate integrin family members on a variety of cell types (Milner and Campbell, 2003;Nakao et al, 2003) so we used a gene expression profiling system to compare the integrin expression pattern in wt and TNF-a À/À keratinocytes in vitro.…”

Section: Mmp-9 Protein Accumulates In Interfollicular Epidermis Durinmentioning

confidence: 99%

TNF-α regulates epithelial expression of MMP-9 and integrin αvβ6 during tumour promotion. A role for TNF-α in keratinocyte migration?

et al. 2004

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Mice deficient in TNF-a (TNF-a À/À mice) are resistant to skin carcinogenesis and expression of MMP-9 is inhibited in TNF-a À/À mice during skin tumour development. In the early stages of tumour promotion, MMP-9 protein initially localized to the follicular epidermis but subsequently began to accumulate in the interfollicular epidermis of wild-type but not TNF-a À/À mice. Inhibition of TNF-a or MMP-9 function reduced keratinocyte migration in vitro. In addition, a deficiency of TNF-a delayed re-epithelialization in vivo and this correlated with reduced MMP-9 expression. Collectively, these data suggest that MMP-9 regulates keratinocyte migration in a TNF-a-dependent manner. Expression profiling of genes that control cell adhesion and migration revealed markedly lower levels of the integrin subunits av and b6 in TNF-a À/À compared with wild-type keratinocytes in vitro. avb6 expression was upregulated by keratinocytes in vitro and during tumour promotion in vivo in a TNF-adependent manner. Furthermore, avb6 blockade significantly inhibited keratinocyte migration and TNFa-stimulated MMP-9 expression in vitro. These data illustrate a novel TNF-a-dependent mechanism for the control of avb6 expression and suggest one pathway for TNF-a regulation of MMP-9. Increased MMP-9 and avb6 expression may stimulate epithelial cell migration during tumour formation and may be one mechanism whereby TNF-a acts as an endogenous tumour promoter.

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Synergistic Effect of TNF-α in Soluble VCAM-1-Induced Angiogenesis Through α4 Integrins

Cited by 76 publications

References 48 publications

Direct inhibition of EGF receptor activation in vascular endothelial cells by gefitinib (‘Iressa’, ZD1839)

Direct inhibition of EGF receptor activation in vascular endothelial cells by gefitinib (‘Iressa’, ZD1839)

Pharmacoproteomic Analysis of a Novel Cell-permeable Peptide Inhibitor of Tumor-induced Angiogenesis

TNF-α regulates epithelial expression of MMP-9 and integrin αvβ6 during tumour promotion. A role for TNF-α in keratinocyte migration?

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