Enhanced tumour cell nuclear targeting in a tumour progression model

Nastasie, Michael S; Thissen, Helmut; Jans, David A.; Wagstaff, Kylie M.

doi:10.1186/s12885-015-1045-z

Cited by 5 publications

(4 citation statements)

References 51 publications

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“…Sections of RM aorta or carotid atherosclerotic plaques were imaged by fluorescence microscopy and analyzed using ImageJ software (NIH), with iterative deconvolution methods (up to 10 iterations) to enhance and study high-resolution images. Target to nuclear fluorescence ratio (Fc/n) was determined according to the formula: Fc/n = (Fc-Fb)/(Fn-Fb), where Fb is background auto-fluorescence [ 26 ].…”

Section: Methodsmentioning

confidence: 99%

CX3CL1 and IL-15 Promote CD8 T cell chemoattraction in HIV and in atherosclerosis

et al. 2020

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Atherosclerotic cardiovascular disease (ASCVD) remains an important cause of morbidity in the general population and risk for ASCVD is increased approximately 2-fold in persons living with HIV infection (PLWH). This risk is linked to elevated CD8 T cell counts that are abundant in atherosclerotic plaques and have been implicated in disease pathogenesis yet the mechanisms driving T cell recruitment to and activation within plaques are poorly defined. Here we investigated the role of CD8 T cells in atherosclerosis in a non-human primate model of HIV infection and in the HIV-uninfected elderly; we sought to identify factors that promote the activation, function, and recruitment to endothelium of CX3CR1+ CD8 T cells. We measured elevated expression of CX3CL1 and IL-15, and increased CD8 T cell numbers in the aortas of rhesus macaques infected with SIV or SHIV, and demonstrated similar findings in atherosclerotic vessels of HIV-uninfected humans. We found that recombinant TNF enhanced the production and release of CX3CL1 and bioactive IL-15 from aortic endothelial cells, but not from aortic smooth muscle cells. IL-15 in turn promoted CX3CR1 surface expression on and TNF synthesis by CD8 T cells, and IL-15-treated CD8 T cells exhibited enhanced CX3CL1-dependent chemoattraction toward endothelial cells in vitro.

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Section: Methodsmentioning

confidence: 99%

CX3CL1 and IL-15 Promote CD8 T cell chemoattraction in HIV and in atherosclerosis

et al. 2020

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“…The representative numerical fluorescence intensity values were measured for the respective target signal and DAPI. We determined the target to nuclear fluorescence ratio (Fc/n) according to the formula Fc/n = (Fc-Fb)/(Fn-Fb), where Fb is background autofluorescence (45). We also applied iterative deconvolution methods (up to 10 iterations) to enhance and study high-resolution images.…”

Section: Microscopy and Image Analysismentioning

confidence: 99%

Cytomegalovirus Coinfection Is Associated with Increased Vascular-Homing CD57+ CD4 T Cells in HIV Infection

Chen

Morris

Panigrahi

et al. 2020

The Journal of Immunology

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Cytotoxic CD4 T cells are linked to cardiovascular morbidities and accumulate in both HIV and CMV infections, both of which are associated with increased risk of cardiovascular disease (CVD). In this study, we identify CMV coinfection as a major driver of the cytotoxic phenotype, characterized by elevated CD57 expression and reduced CD28 expression, in circulating CD4 T cells from people living with HIV infection, and investigate potential mechanisms linking this cell population to CVD. We find that human CD57 + CD4 T cells express high levels of the costimulatory receptor CD2 and that CD2/LFA-3 costimulation results in a more robust and polyfunctional effector response to TCR signals, compared with CD28-mediated costimulation. CD57 + CD4 T cells also express the vascular endothelium-homing receptor CX3CR1 and migrate toward CX3CL1-expressing endothelial cells in vitro. IL-15 promotes the cytotoxic phenotype, elevates CX3CR1 expression, and enhances the trafficking of CD57 + CD4 T cells to endothelium and may therefore be important in linking these cells to cardiovascular complications. Finally, we demonstrate the presence of activated CD57 + CD4 T cells and expression of CX3CL1 and LFA-3 in atherosclerotic plaque tissues from HIVuninfected donors. Our findings are consistent with a model in which cytotoxic CD4 T cells contribute to CVD in HIV/CMV coinfection and in atherosclerosis via CX3CR1-mediated trafficking and CD2/LFA-3-mediated costimulation. This study identifies several targets for therapeutic interventions and may help bridge the gap in understanding how CMV infection and immunity are linked to increased cardiovascular risk in people living with HIV infection.

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“…Also called tumor cell enhanced nuclear targeting site (tNTS), it is responsible for nuclear localization of Apoptin in cancer cells, and has ∼20% of pro-apoptotic activity ( Poon et al, 2005a , b ; Kuusisto et al, 2008 ; Maddika et al, 2009 ; Nastasie et al, 2015 ). It is made up of following subdomains ( Danen-van Oorschot et al, 2003 ; Poon et al, 2005a , b ).…”

Section: Structural Domainsmentioning

confidence: 99%

Apoptin as a Tumor-Specific Therapeutic Agent: Current Perspective on Mechanism of Action and Delivery Systems

Malla

Arora

Khan

et al. 2020

Front. Cell Dev. Biol.

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Cancer remains one of the leading causes of death worldwide in humans and animals. Conventional treatment regimens often fail to produce the desired outcome due to disturbances in cell physiology that arise during the process of transformation. Additionally, development of treatment regimens with no or minimum side-effects is one of the thrust areas of modern cancer research. Oncolytic viral gene therapy employs certain viral genes which on ectopic expression find and selectively destroy malignant cells, thereby achieving tumor cell death without harming the normal cells in the neighborhood. Apoptin, encoded by Chicken Infectious Anemia Virus’ VP3 gene, is a proline-rich protein capable of inducing apoptosis in cancer cells in a selective manner. In normal cells, the filamentous Apoptin becomes aggregated toward the cell margins, but is eventually degraded by proteasomes without harming the cells. In malignant cells, after activation by phosphorylation by a cancer cell-specific kinase whose identity is disputed, Apoptin accumulates in the nucleus, undergoes aggregation to form multimers, and prevents the dividing cancer cells from repairing their DNA lesions, thereby forcing them to undergo apoptosis. In this review, we discuss the present knowledge about the structure of Apoptin protein, elaborate on its mechanism of action, and summarize various strategies that have been used to deliver it as an anticancer drug in various cancer models.

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Enhanced tumour cell nuclear targeting in a tumour progression model

Cited by 5 publications

References 51 publications

CX3CL1 and IL-15 Promote CD8 T cell chemoattraction in HIV and in atherosclerosis

CX3CL1 and IL-15 Promote CD8 T cell chemoattraction in HIV and in atherosclerosis

Cytomegalovirus Coinfection Is Associated with Increased Vascular-Homing CD57+ CD4 T Cells in HIV Infection

Apoptin as a Tumor-Specific Therapeutic Agent: Current Perspective on Mechanism of Action and Delivery Systems

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