Showing papers by "Walter Malorni published in 2006"
TL;DR: It is shown that human metastatic melanoma cells may eat live T cells, which are instead programmed to kill them, suggesting a novel mechanism of tumor immune escape.
Abstract: The phenomenon of cell cannibalism, which generally refers to the engulfment of cells within other cells, was described in malignant tumors, but its biological significance is still largely unknown. In the present study, we investigated the occurrence, the in vivo relevance, and the underlying mechanisms of cannibalism in human melanoma. As first evidence, we observed that tumor cannibalism was clearly detectable in vivo in metastatic lesions of melanoma and often involved T cells, which could be found in a degraded state within tumor cells. Then, in vitro experiments confirmed that cannibalism of T cells was a property of metastatic melanoma cells but not of primary melanoma cells. In particular, morphologic analyses, including time-lapse cinematography and electron microscopy, revealed a sequence of events, in which metastatic melanoma cells were able to engulf and digest live autologous melanoma-specific CD8(+) T cells. Importantly, this cannibalistic activity significantly increased metastatic melanoma cell survival, particularly under starvation condition, supporting the evidence that tumor cells may use the eating of live lymphocytes as a way to "feed" in condition of low nutrient supply. The mechanism underlying cannibalism involved a complex framework, including lysosomal protease cathepsin B activity, caveolae formation, and ezrin cytoskeleton integrity and function. In conclusion, our study shows that human metastatic melanoma cells may eat live T cells, which are instead programmed to kill them, suggesting a novel mechanism of tumor immune escape. Moreover, our data suggest that cannibalism may represent a sort of "feeding" activity aimed at sustaining survival and progression of malignant tumor cells in an unfavorable microenvironment.
253 citations
TL;DR: A brief review that takes into account the possible implications of redox-associated alterations of red blood cells in determining their function and fate is summarized.
Abstract: Red blood cells may exert both an antioxidant and a prooxidant activity. The first is exerted in physiologic conditions, whereas the second can be detected in several human pathologies. These opposite characteristics can depend on the environmental milieu as well as on intrinsic alterations. Both these aspects are summarized in this brief review that takes into account the possible implications of redox-associated alterations of red blood cells in determining their function and fate.
34 citations
TL;DR: The present work underlines the possibility that HD‐associated mitochondrial defects could tentatively be by‐passed by the cells by activating cellular ‘phagic’ activities, including so‐called ‘mitophagy’ and ‘cannibalism’, that only finally lead to cell death.
Abstract: In the present work, we studied the mitochondrial function and cell death pathway(s) in heterozygous and homozygous immortalized cell lines from patients with Huntington's disease (HD). Heterozygosis was characterized by specific alterations in mitochondrial membrane potential, a constitutive hyperpolarization state of mitochondria, and was correlated with an increased susceptibility to apoptosis. Lymphoblasts from homozygous patients, on the other hand, were characterized by a significant percentage of cells displaying autophagic vacuoles. These cells also demonstrated a striking attitude towards significant cannibalistic activity. Considering the pathogenic role of cell death in HD, our study provides new and useful insights into the role of mitochondrial dysfunction, i.e. hyperpolarization, in hijacking HD heterozygous cells towards apoptosis and HD homozygous cells towards a peculiar phenotype characterized by both self- and xeno-cannibalism. These events can, however, be viewed as an ultimate attempt to survive rather than a way to die. The present work underlines the possibility that HD-associated mitochondrial defects could tentatively be by-passed by the cells by activating cellular 'phagic' activities, including so-called 'mitophagy' and 'cannibalism', that only finally lead to cell death.
34 citations
TL;DR: It is reported here for the first time that the Rac‐activating toxin CNF1 interferes with the occurrence of MC and leads to aneuploidy and multinucleation, which seems to be in line with the anti‐apoptotic activity of the toxin and consistent with the hypothesis that points at C NF1 as a toxin bearing a carcinogenic potential.
Abstract: The term mitotic catastrophe (MC) was coined to describe the mammalian cell death caused by aberrant mitosis. MC occurs with features that are fundamentally different from those typifying other forms of cell death, including apoptosis. We report here for the first time that the Rac-activating toxin CNF1 interferes with the occurrence of MC and leads to aneuploidy and multinucleation. This seems to be in line with the anti-apoptotic activity of the toxin and consistent with the hypothesis that points at CNF1 as a toxin bearing a carcinogenic potential.
33 citations
TL;DR: The results suggest that the reinforcement of the actin cytoskeleton induced by A3 receptor agonists is mediated by an interference with the activation/inactivation cycle of Rho proteins, which may represent a biological target for the identification of novel neuroprotective strategies.
Abstract: In previous studies, we have demonstrated that exposure of astroglial cells to A3 adenosine receptor agonists results in dual actions on cell survival, with "trophic" and antiapoptotic effects at nanomolar concentrations and induction of cell death at micromolar agonist concentrations. The protective actions of A3 agonists have been associated with a reinforcement of the actin cytoskeleton, which likely results in increased resistance of cells to cytotoxic stimuli. The molecular mechanisms at the basis of this effect and the signalling pathway(s) linking the A3 receptor to the actin cytoskeleton have never been elucidated. Based on previous literature data suggesting that the actin cytoskeleton is controlled by small GTP-binding proteins of the Rho family, in the study reported here we investigated the involvement of these proteins in the effects induced by A3 agonists on human astrocytoma ADF cells. The presence of the A3 adenosine receptor in these cells has been confirmed by immunoblotting analysis. As expected, exposure of human astrocytoma ADF cells to nanomolar concentrations of the selective A3 agonist 2-chloro-N6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (CI-IB-MECA) resulted in formation of thick actin positive stress fibers. Preexposure of cells to the C3B toxin that inactivates Rho-proteins completely prevented the actin changes induced by CI-IB-MECA. Exposure to the A3 agonist also resulted in significant reduction of Rho-GDI, an inhibitory protein known to maintain Rho proteins in their inactive state, suggesting a potentiation of Rho-mediated effects. This effect was fully counteracted by the concomitant exposure to the selective A3 receptor antagonist MRS1191. These results suggest that the reinforcement of the actin cytoskeleton induced by A3 receptor agonists is mediated by an interference with the activation/inactivation cycle of Rho proteins, which may, therefore, represent a biological target for the identification of novel neuroprotective strategies.
33 citations
TL;DR: Taking into account the complex role of bacterial protein toxins in the infectious processes, the CNF1 activity is indicated as a Janus-faced paradigm of those bacteria that hijack cell fate to their own benefit, linked to the hypothesized connection between certain bacterial toxins and cancer onset.
Abstract: Cytotoxic necrotizing factor 1 is a bacterial protein toxin from Escherichia coli that is able to activate the Rho GTPases and to hinder apoptosis and mitotic catastrophe. Upon exposure to toxin, cells undergo a complex framework of changes, including cytoskeleton remodeling and multinucleation. These cells also show a high survival rate for long periods of time and improve both their macropinocytotic scavenging activities and microautophagy. Only at the very end, probably when “feeding” materials are exhausted, they do these cells die by autophagy. Taking into account the complex role of bacterial protein toxins in the infectious processes, we indicate the CNF1 activity as a Janus-faced paradigm of those bacteria that hijack cell fate to their own benefit. This could somehow be linked to the hypothesized connection between certain bacterial toxins and cancer onset.Addendum to:Is the Rac GTPase-Activating Toxin CNF1 a Smart Hijacker of Host Cell Fate?W. Malorni and C. FiorentiniFASEB J 2006; 20:606-9
9 citations
TL;DR: Findings strengthen the role of Rac‐1 molecule in the induction of DC differentiation and suggest that, besides its activation, the upregulation of Rac-1 molecule might also play a role in the acquisition of DC mature phenotype.
5 citations
Patent•
03 Aug 2006
TL;DR: The use of dermonecrotizing protein factors of bacterial origin, particularly from Escherichia coli and related uses in medical field is discussed in this paper, where the authors discuss new uses in the medical field of the protein factors.
Abstract: The invention concerns new uses in medical field of the dermonecrotizing protein factors of bacterial origin, particularly from Escherichia coli and related uses in medical field
1 citations
Patent•
03 Aug 2006