Angiogenic potential in vivo by Kaposiʼs sarcoma cell-free supernatants and HIV-1 tat product: inhibition of KS-like lesions by tissue inhibitor of metalloproteinase-2

Albini, Adriana; Fontanini, Gabriella; Masiello, Luciana; Tacchetti, Carlo; Bigini, D; Luzzi, Paola; Noonan, Douglas M.; Stetler-Stevenson, William G.

doi:10.1097/00002030-199409000-00004

Cited by 145 publications

(106 citation statements)

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“…The Matrigel sponge model of angiogenesis was utilized as previously described. 34 Angiogenic growth factors were added to unpolymerized liquid matrigel at 41C. This suspension (final volume 600 ml) will slowly injected subcutaneously into the flank of mice where the matrigel polymerizes to form a solid gel.…”

Section: Methodsmentioning

confidence: 99%

Prevention of angiogenesis by naked DNA IL-12 gene transfer: angioprevention by immunogene therapy

et al. 2004

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IL-12 is thought to induce a cytokine cascade with antiangiogenic effects mediated by IFN-g and angiostatic CXCR3 chemokine ligands. Naked DNA intramuscular injection of an expression vector plasmid producing IL-12 resulted in significant, well-tolerated elevation of serum IL-12 levels. Injection of the IL-12 plasmid at least 2 days, and up to 20 days, before subcutaneous injection of matrigel with angiogenic factors resulted in strong prevention of angiogenesis in both C57/bl and nude mice. A single injection of the IL-12 plasmid contemporarily with the matrigel or 2 days after resulted in partial, statistically not significant, inhibition. Control plasmid injection did not affect either angiogenesis or angiogenesis inhibition by IL-12 protein in vivo. Angiogenesis inhibition was observed in NK cell-depleted C57/bl and nude mice as well as in IFN-g À/À and CXCR3 À/À knockout mice, indicating that NK-and/or T-cell-initiated IFN-gchemokine cascades were not involved in the angiogenesis inhibition observed in vivo. Finally, IL-12 plasmid DNA gene transfer significantly prevented the growth and vascularization of highly angiogenic KS-Imm Kaposi's sarcoma and TS/ A murine mammary carcinoma tumors in nude and/or syngeneic mice. These data suggest that a preventive gene therapy approach using antiangiogenic cytokines can effectively inhibit tumor angiogenesis and KS, representing an example of angioimmunoprevention.

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Section: Methodsmentioning

confidence: 99%

Prevention of angiogenesis by naked DNA IL-12 gene transfer: angioprevention by immunogene therapy

et al. 2004

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“…The Matrigel sponge model of angiogenesis was used as previously described (26). Angiogenic growth factors, including vascular endothelial growth factor (100 ng/ml), TNF-␣ (2 ng/ml), and heparin (24 -26 U/ml) (VTH; all from PeproTech), were added to liquid Matrigel at 4°C.…”

Section: Angiogenesis Assaymentioning

confidence: 99%

Identification of Genes Selectively Regulated by IFNs in Endothelial Cells

Indraccolo

Pfeffer

Minuzzo

et al. 2007

The Journal of Immunology

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IFNs are highly pleiotropic cytokines also endowed with marked antiangiogenic activity. In this study, the mRNA expression profiles of endothelial cells (EC) exposed in vitro to IFN-α, IFN-β, or IFN-γ were determined. We found that in HUVEC as well as in other EC types 175 genes were up-regulated (>2-fold increase) by IFNs, including genes involved in the host response to RNA viruses, inflammation, and apoptosis. Interestingly, 41 genes showed a >5-fold higher induction by IFN-α in EC compared with human fibroblasts; among them, the gene encoding the angiostatic chemokine CXCL11 was selectively induced by IFN-α in EC along with other genes associated with angiogenesis regulation, including CXCL10, TRAIL, and guanylate-binding protein 1. These transcriptional changes were confirmed and extended by quantitative PCR analysis and ELISA; whereas IFN-α and IFN-β exerted virtually identical effects on transcriptome modulation, a differential gene regulation by type I and type II IFN emerged, especially as far as quantitative aspects were concerned. In vivo, IFN-α-producing tumors overexpressed murine CXCL10 and CXCL11, guanylate-binding protein 1, and TRAIL, with evidence of CXCL11 production by tumor-associated EC. Overall, these findings improve our understanding of the antiangiogenic effects of IFNs by showing that these cytokines trigger an antiangiogenic transcriptional program in EC. Moreover, we suggest that quantitative differences in the magnitude of the transcriptional activation of IFN-responsive genes could form the basis for cell-specific transcriptional signatures.

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“…The s.c. Matrigel sponge model of angiogenesis in vivo was used (23). Briefly, liquid Matrigel containing heparin (26 U/ml; Schwarz Pharma, San Grato-Lodi, Italy) was mixed at 4°C with or without proangiogenic agonists, including a potent angiogenic mixture consisting of human or murine VEGF-A (60 ng/ml) plus murine TNF-␣ (2 ng/ml; PeproTech; VEGF-A/ TNF-␣/heparin (VTH), 2 ng/ml TNF-␣, or either 80 ng/ml CXCL1/MIP-2 or 80 ng/ml CXCL1/KC (R&D Systems), and then diluted to a final volume of 0.6 ml.…”

Section: In Vivo Angiogenesismentioning

confidence: 99%

CXCL1/Macrophage Inflammatory Protein-2-Induced Angiogenesis In Vivo Is Mediated by Neutrophil-Derived Vascular Endothelial Growth Factor-A

Scapini

Morini

Tecchio

et al. 2004

The Journal of Immunology

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223

172

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The angiogenic activity of CXC-ELR+ chemokines, including CXCL8/IL-8, CXCL1/macrophage inflammatory protein-2 (MIP-2), and CXCL1/growth-related oncogene-α in the Matrigel sponge angiogenesis assay in vivo, is strictly neutrophil dependent, as neutrophil depletion of the animals completely abrogates the angiogenic response. In this study, we demonstrate that mice deficient in the src family kinases, Hck and Fgr (hck−/−fgr−/−), are unable to develop an angiogenic response to CXCL1/MIP-2, although they respond normally to vascular endothelial growth factor-A (VEGF-A). Histological examination of the CXCL1/MIP-2-containing Matrigel implants isolated from wild-type or hck−/−fgr−/− mice showed the presence of an extensive neutrophil infiltrate, excluding a defective neutrophil recruitment into the Matrigel sponges. Accordingly, neutrophils from hck−/−fgr−/− mice normally migrated and released gelatinase B in response to CXCL1/MIP-2 in vitro, similarly to wild-type neutrophils. However, unlike wild-type neutrophils, those from hck−/−fgr−/− mice were completely unable to release VEGF-A upon stimulation with CXCL1/MIP-2. Furthermore, neutralizing anti-VEGF-A Abs abrogated the angiogenic response to CXCL1/MIP-2 in wild-type mice and CXCL1/MIP-2 induced angiogenesis in the chick embryo chorioallantoic membrane assay, indicating that neutrophil-derived VEGF-A is a major mediator of CXCL1/MIP-2-induced angiogenesis. Finally, in vitro kinase assays confirmed that CXCL1/MIP-2 activates Hck and Fgr in murine neutrophils. Taken together, these data demonstrate that CXCL1/MIP-2 leads to recruitment of neutrophils that, in turn, release biologically active VEGF-A, resulting in angiogenesis in vivo. Our observations delineate a novel mechanism by which CXCL1/MIP-2 induces neutrophil-dependent angiogenesis in vivo.

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Angiogenic potential in vivo by Kaposiʼs sarcoma cell-free supernatants and HIV-1 tat product: inhibition of KS-like lesions by tissue inhibitor of metalloproteinase-2

Cited by 145 publications

References 0 publications

Prevention of angiogenesis by naked DNA IL-12 gene transfer: angioprevention by immunogene therapy

Prevention of angiogenesis by naked DNA IL-12 gene transfer: angioprevention by immunogene therapy

Identification of Genes Selectively Regulated by IFNs in Endothelial Cells

CXCL1/Macrophage Inflammatory Protein-2-Induced Angiogenesis In Vivo Is Mediated by Neutrophil-Derived Vascular Endothelial Growth Factor-A

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