Interferon-β gene transfer inhibits melanoma cells adhesion and migration

Rossi, Ursula Amaranta; Finocchiaro, Liliana M.E.; Glikin, Gerardo C.

doi:10.1016/j.cyto.2015.11.012

Cited by 8 publications

(5 citation statements)

References 43 publications

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“…Decitabine Improves Anti-Tumor Activity of Type I Interferons similar to a previous study using repeated administrations of DAC (over 4 consecutive days) followed by IFN-a2b (Reu et al, 2006). In addition, DAC/IFN-I also inhibited the migration/motility of melanoma cells, in accordance with previous reports showing reduced migration and motility in melanoma cells overexpressing IFN-b (Rossi et al, 2015). DAC/IFN-I effectively suppressed both the formation and expansion of three-dimensional human melanoma spheroids in a synergistic manner.…”

Section: Discussionsupporting

confidence: 90%

Combining Type I Interferons and 5-Aza-2′-Deoxycitidine to Improve Anti-Tumor Response against Melanoma

Lucarini

Buccione

Ziccheddu

et al. 2017

Journal of Investigative Dermatology

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Resistance to IFN-I-induced antineoplastic effects has been reported in many tumors and arises, in part, from epigenetic silencing of IFN-stimulated genes by DNA methylation. We hypothesized that restoration of IFN-stimulated genes by co-administration of the demethylating drug 5-aza-2'-deoxycitidine (decitabine [DAC]) may enhance the susceptibility to IFN-I-mediated antitumoral effects in melanoma. We show that combined administration of IFN-I and DAC significantly inhibits the growth of murine and human melanoma cells, both in vitro and in vivo. Compared with controls, DAC/IFN-I-treated melanoma cells exhibited reduced cell growth, augmented apoptosis, and diminished migration. Moreover, IFN-I and DAC synergized to suppress the growth of three-dimensional human melanoma spheroids, altering tumor architecture. These direct antitumor effects correlated with induction of the IFN-stimulated gene Mx1. In vivo, DAC/IFN-I significantly reduced melanoma growth via stimulation of adaptive immunity, promoting tumor-infiltrating CD8 T cells while inhibiting the homing of immunosuppressive CD11b myeloid cells and regulatory T cells. Accordingly, exposure of human melanoma cells to DAC/IFN-I induced the recruitment of immune cells toward the tumor in a Matrigel (Corning Life Sciences, Kennebunkport, ME)-based microfluidic device. Our findings underscore a beneficial effect of DAC plus IFN-I combined treatment against melanoma through both direct and immune-mediated anti-tumor effects.

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Section: Discussionsupporting

confidence: 90%

Combining Type I Interferons and 5-Aza-2′-Deoxycitidine to Improve Anti-Tumor Response against Melanoma

Lucarini

Buccione

Ziccheddu

et al. 2017

Journal of Investigative Dermatology

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“…However, the migration and invasion properties of glioma cells are affected by interferon-regulated genes (Yu et al 2011 ; Tarassishin and Lee 2013 ) and neuronal survival seems to require a basic level of interferon signaling (Ejlerskov et al 2015 ). Moreover, interference of IFNβ with migration has been shown especially in the leukocyte lineage of cells (Lou et al 1999 ; Staun-Ram and Miller 2011 ; Floris et al 2002 ) and for various tumor cells (Booy et al 2015 ; Rossi et al 2015 ). Many of these studies suggest that cell migration may be affected by interferons through a reduced secretion of matrix metalloproteases (Stuve et al 1997 ; Yen et al 2010 ).…”

Section: Discussionmentioning

confidence: 99%

Impairment of human neural crest cell migration by prolonged exposure to interferon-beta

et al. 2017

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Human cell-based toxicological assays have been used successfully to detect known toxicants, and to distinguish them from negative controls. However, there is at present little experience on how to deal with hits from screens of compounds with yet unknown hazard. As a case study to this issue, we characterized human interferon-beta (IFNβ) as potential developmental toxicant affecting neural crest cells (NCC). The protein was identified as a hit during a screen of clinically used drugs in the ‘migration inhibition of neural crest’ (MINC) assay. Concentration–response studies in the MINC combined with immunocytochemistry and mRNA quantification of cellular markers showed that IFNβ inhibited NCC migration at concentrations as low as 20 pM. The effective concentrations found here correspond to levels found in human plasma, and they were neither cytostatic nor cytotoxic nor did they did they affect the differentiation state and overall phenotype of NCC. Data from two other migration assays confirmed that picomolar concentration of IFNβ reduced the motility of NCC, while other interferons were less potent. The activation of JAK kinase by IFNβ, as suggested by bioinformatics analysis of the transcriptome changes, was confirmed by biochemical methods. The degree and duration of pathway activation correlated with the extent of migration inhibition, and pharmacological block of this signaling pathway before, or up to 6 h after exposure to the cytokine prevented the effects of IFNβ on migration. Thus, the reduction of vital functions of human NCC is a hitherto unknown potential hazard of endogenous or pharmacologically applied interferons.Electronic supplementary materialThe online version of this article (doi:10.1007/s00204-017-1966-1) contains supplementary material, which is available to authorized users.

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“…82 Of note, at least in some settings such a cytoprotective effect could be attributed to the upregulation or stabilization of antiapoptotic proteins such as BCL2 apoptosis regulator (BCL2) and MCL1 apoptosis regulator, BCL2 family member (MCL1). 79,82 Intriguingly, type I IFN responses have also been linked to decreased cancer cell motility upon reduced interactions with the extracellular matrix (ECM), 83 suppressed neoangiogenesis upon vascular endothelial growth factor A (VEGFA) downregulation, 84 but improved cancer cell bioenergetic metabolism. 85 Thus, type I IFN responses appear to have a context-dependent impact on cancer cell proliferation, survival, and invasiveness.…”

Section: An Cer Cell-intrin S I C Effec Ts Of T Ype I Ifnmentioning

confidence: 99%

“…Intriguingly, type I IFN responses have also been linked to decreased cancer cell motility upon reduced interactions with the extracellular matrix (ECM), 83 suppressed neoangiogenesis upon vascular endothelial growth factor A (VEGFA) downregulation, 84 but improved cancer cell bioenergetic metabolism 85 . Thus, type I IFN responses appear to have a context‐dependent impact on cancer cell proliferation, survival, and invasiveness.…”

Section: Cancer Cell‐intrinsic Effects Of Type I Ifnmentioning

confidence: 99%

Type I interferon and cancer

Holicek,

Guilbaud,

Klapp

et al. 2023

Immunological Reviews

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SummaryType I interferon (IFN) is a class of proinflammatory cytokines with a dual role on malignant transformation, tumor progression, and response to therapy. On the one hand, robust, acute, and resolving type I IFN responses have been shown to mediate prominent anticancer effects, reflecting not only their direct cytostatic/cytotoxic activity on (at least some) malignant cells, but also their pronounced immunostimulatory functions. In line with this notion, type I IFN signaling has been implicated in the antineoplastic effects of various immunogenic therapeutics, including (but not limited to) immunogenic cell death (ICD)‐inducing agents and immune checkpoint inhibitors (ICIs). On the other hand, weak, indolent, and non‐resolving type I IFN responses have been demonstrated to support tumor progression and resistance to therapy, reflecting the ability of suboptimal type I IFN signaling to mediate cytoprotective activity, promote stemness, favor tolerance to chromosomal instability, and facilitate the establishment of an immunologically exhausted tumor microenvironment. Here, we review fundamental aspects of type I IFN signaling and their context‐dependent impact on malignant transformation, tumor progression, and response to therapy.

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Interferon-β gene transfer inhibits melanoma cells adhesion and migration

Cited by 8 publications

References 43 publications

Combining Type I Interferons and 5-Aza-2′-Deoxycitidine to Improve Anti-Tumor Response against Melanoma

Combining Type I Interferons and 5-Aza-2′-Deoxycitidine to Improve Anti-Tumor Response against Melanoma

Impairment of human neural crest cell migration by prolonged exposure to interferon-beta

Type I interferon and cancer

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