Inhibition of Cell Motility by Interferon

Brouty‐Boyé, Danièle; Zetter, Bruce R.

doi:10.1126/science.6154315

Cited by 297 publications

(108 citation statements)

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“…These findings support the hypothesis that the antiangiogenic effect of IFN-g on human endothelial cells required other mechanisms besides apoptosis. Human IFN-g inhibits endothelial migration and proliferation (Brouty-Boye and Zetter, 1980;Friesel et al, 1987;Tsuruoka et al, 1988;Albini et al, 2000) and has strong antiproliferative effects on NB tumour cells (Ponzoni et al, 1992;Airoldi et al, 2004), from which the human endothelial cells derived. Thus, the antiangiogenic effect was likely due to a combination of apoptosis and reduced proliferation.…”

Section: Discussionmentioning

confidence: 99%

Angiogenesis in a human neuroblastoma xenograft model: mechanisms and inhibition by tumour-derived interferon-γ

et al. 2006

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Tumour progression in neuroblastoma (NB) patients correlates with high vascular index. We have previously shown that the ACN NB cell line is tumorigenic and angiogenic in immunodeficient mice, and that interferon-g (IFN-g) gene transfer dampens ACN tumorigenicity. As IFN-g represses lymphocyte-induced tumour angiogenesis in various murine models and inhibits proliferation and migration of human endothelial cells, we have investigated the antiangiogenic activity of tumour-derived IFN-g and the underlying mechanism(s). In addition, we characterised the tumour vasculature of the ACN xenografts, using the chick embryo chorioallantoic membrane assay. We show that the ACN/IFN-g xenografts had a lower microvessel density and less in vivo angiogenic potential than the vector-transfected ACN/neo. The vascular channels of both xenografts were formed by a mixed endothelial cell population of murine and human origin, as assessed by the FICTION (fluorescence immunophenotyping and interphase cytogenetics) technique. With respect to ACN/neo, the ACN/IFN-g xenografts showed more terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling-positive human and murine endothelial cells, suggesting that inhibition of angiogenesis by IFN-g was dependent on the induction of apoptosis, likely mediated by nitric oxide. Once the dual origin of tumour vasculature is confirmed in NB patients, the xenograft model described here will prove useful in testing the efficacy of different antiangiogenic compounds.

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Section: Discussionmentioning

confidence: 99%

Angiogenesis in a human neuroblastoma xenograft model: mechanisms and inhibition by tumour-derived interferon-γ

et al. 2006

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“…As early as 1980, IFN had been shown to inhibit endothelial cell motility [58], and later in the 1980s was shown to inhibit tumor-and allogeneic lymphocyte-induced angiogenesis [59] and to selectively damage the tumor microvascular endothelium, leading to coagulation necrosis of murine tumors selected for resistance to IFN's antiproliferative effects [60]. Further investigations of the angiogenesis inhibitory activities of IFN in the 1990s showed that IFNα could downregulate IL-8 production in fibroblasts [61] and bFGF in human tumor cell lines resistant to IFN's antiproliferative effects [62].…”

Section: Angiogenesis Inhibitionmentioning

confidence: 99%

AIDS-associated Kaposi's sarcoma: Is there still a role for interferon alfa?

Krown

2007

Cytokine & Growth Factor Reviews

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Interferon alfa (IFNA) was one of the first agents to be used therapeutically in AIDS-associated Kaposi's sarcoma (KS) more than 25 years ago, and induces tumor regression in a subset of patients. Although much has been learned about the clinical role of IFNα in KS treatment, little is currently known about the mechanism(s) by which IFNA causes KS regression. This is despite a growing understanding of both KS pathogenesis and relevant IFNA activities. To a large extent other agents have supplanted IFNA as treatments for KS, but there may still remain a therapeutic role for IFNA, possibly in combination with other agents targeting angiogenesis and/or HHV-8-encoded human gene homologs that encode proteins involved in cell cycle regulation and signaling. KeywordsInterferon; Kaposi's sarcoma In 1995, when I was honored as a recipient of the ISICR Milstein Award, the AIDS epidemic had recently begun its 15 th year and the human immunodeficiency virus (HIV-1) had been isolated some 12 years previously [1]. However, the virus associated with Kaposi's sarcoma (KS), the most common AIDS-associated malignancy, had been described less than a year earlier [2], its significance was still in some question and its role in KS development had not been characterized, and the active combination drug regimens with which we now treat HIV infection had not yet become widely available. Recombinant interferon alfa preparations (IFNα2a and IFNα2b), which had received approval from the U.S. Food and Drug Administration (FDA) for treatment of AIDS-associated KS in 1988, were still the only approved drugs for systemic treatment of KS (the chemotherapeutic agent, liposomal doxorubicin, would receive FDA approval later in 1995, as did liposomal daunorubicin in 1996 and paclitaxel in 1997). Now, more than a quarter century after the first published reports describing AIDS and its association with KS [3-6] and our first modestly successful attempts to treat KS with IFNα [7], this agent is used infrequently to treat KS, although it still finds use in HIV-infected individuals co-infected with hepatitis C. In this brief review, I will summarize some of the history of IFNα in the treatment of AIDS-associated KS, concentrating on examples of clinical trials in which I have personally been involved, and consider whether there remains a potentially valuable role for this agent in KS treatment.

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“…28,29 Moreover, IFN-␣ was the first of the known angiogenesis inhibitors to be evaluated clinically and to show its therapeutic potential in angiogenic diseases, such as childhood hemangioma and Kaposi's sarcoma. 30,31 Its anti-angiogenic activity has been well established by a number of in vitro studies indicating that it can block endothelial cell migration, 8,32 and also downregulate angiogenic factor expression, such as bFGF, IL-8, MMP-2 and MMP-9. [33][34][35][36] IFN-␣ also down-regulates bFGF expression in human carcinomas.…”

Section: Figure 7 Angiostatin Expression In Mcf7 and Mda-mb435 Tumorsmentioning

confidence: 99%

“…5,6 IFN-␣ and IFN-␤ are multifunctional regulatory cytokines involved in the control of cell proliferation and viral infections that also show anti-angiogenic activity both in vitro and in vivo. 7,8 Frequent systemic administration of low-dose IFN-␣ and IFN-␤, or the introduction of their genes in some tumor or stromal cells has produced therapeutic effects against many tumor types in several animal models. [9][10][11] Angiostatic therapy appears to require long-term administration of the inhibitor to ensure tumor growth suppression in vivo.…”

Section: Introductionmentioning

confidence: 99%