62 research outputs found
ROS-major mediators of extracellular matrix remodeling during tumor progression
No full textExtracellular matrices (ECMs) represent a complex network of proteins, proteoglycans and glycosaminoglycans (GAGs), composed of independent structural domains, ultimately constituting the cell microenvironment. As a highly organized, insoluble suprastructure, the ECM can, in a spatially patterned and regulated manner, integrate and deliver multiple complex signals to cells that affect their behavior. During the progression of carcinogenesis, tumor cells, through a continually changing interface, remodel and simultaneously interact with the components of ECM, as well as with surrounding stromal cells. Within this complex network of ECM components affecting tumor progression, reactive oxygen species/reactive nitrogen species (ROS/RNS) play a wide emerging role. In this minireview we will focus on the ROS-dependent modulations of tumor ECM and how this in turn affects the insidious pathways of tumor progression and dissemination. (C) 2013 Elsevier Ltd. All rights reserved
Role of oxidative stress in chemical allergens induced skin cells activation
No full textAllergic contact dermatitis (ACD) is an important occupational and environmental disease caused by topical exposure to chemical allergens. It describes the adverse effects that may results when exposure to a chemical elicits a T cell-mediated inflammatory skin disease. The ability of contact sensitizers to induce the oxidative stress pathway in keratinocytes and dendritic cells has been confirmed by several authors. Reactive oxygen species (ROS) can serve as essential second messengers mediating cellular responses resulting in immune cells activation. Oxidative stress may be the starter point, as it leads to the activation of transcription factors and signaling pathways, including NF-kB and p38 MAPK, which leads to the release of cytokines and chemokines. ROS are also involved in the activation of the NLRP3/NALP3 inflammasome, which is required to direct the proteolytic maturation of inflammatory cytokines such as IL-1β and IL-18, which are all integral to the process of dendritic cells mobilization, migration and functional maturation. Moreover, emerging evidence correlates ROS to changes in the constitution of the extracellular microenvironment found to facilitate ACD. The purpose of this review is to provide both conceptual and technical frameworks on the role of oxidative stress in chemical allergy
Data on the putative role of p53 in breast cancer cell adhesion: Technical information for adhesion assay
No full textAbstractIn this data article, the potential role of p53 tumor suppressor gene (p53) on the attachment ability of MCF-7 breast cancer cells was investigated. In our main article, “IGF-I/ EGF and E2 signaling crosstalk through IGF-IR conduit point affect breast cancer cell adhesion” (K. Voudouri, D. Nikitovic, A. Berdiaki, D. Kletsas, N.K. Karamanos, G.N. Tzanakakis, 2016) [1], we describe the key role of IGF-IR in breast cancer cell adhesion onto fibronectin (FN). p53 tumor suppressor gene is a principal regulator of cancer cell proliferation. Various data have demonstrated an association between p53 and IGF-IR actions on cell growth through its’ putative regulation of IGF-IR expression. According to our performed experiments, p53 does not modify IGF-IR expression and does not affect basal MCF-7 cells adhesion onto FN. Moreover, technical details about the performance of adhesion assay onto the FN substrate were provided
HA metabolism in skin homeostasis and inflammatory disease
No full textHyaluronan (HA), an unsulfated glycosaminoglycan, is an important component of the complex extracellular matrix network which surrounds and supports cells in tissues. HA is detected in all vertebrate tissues, but the bulk of HA is produced and deposited in the skin. In this review we focus on the role of HA in skin-associated inflammatory disease and wound healing. Properties of HA are directly dependent on its molecular weight. Thus, high molecular weight HA (HMWHA) is deposited in normal tissues during homeostasis and promotes their stability whereas low molecular weight HA fragments (LMWHA), on the other hand, may arise from enzymatic or chemical activities. The degradation of HMWHA to LMWHA fragments, often leads to the generation of biologically active oligosaccharides with different properties and postulated functions in wound scar formation and inflammation. More detailed studies of HA involvement in skin-associated inflammatory disease may result in novel treatment modalities
Hyaluronan regulates chemical allergen-induced IL-18 production in human keratinocytes
No full textInterleukin-18 (IL-18) has been shown to play a key proximal role in the induction of allergic contact dermatitis. Low molecular weight hyaluronan (LMWHA), an endogenous molecule and a member of the so-called damage associated molecular patterns (DAMPs), has been suggested to elicit immune-stimulatory effects. The purpose of this study was to examine the role of hyaluronan (HA) degradation in IL-18 production in human keratinocytes following stimulation with the contact sensitizers 2,4-dinitrochlorobenzene (DNCB) and PPD. IL-18 production in the human keratinocyte cell line NCTC2544 was measured by ELISA, whereas changes in HA metabolism were determined by Real-time PCR and immunofluorescence. Both contact allergens were able to enhance hyaluronidase (HYAL) 1 and 2 expression inducing HA degradation. Modulation of HA production, by HYAL or aristolochic acid pre-treatment, resulted in a significant reduction of contact allergen-induced IL-18 production. Oxidative stress appears to be the initial step in KC activation, as all the sequels of events can be blocked using antioxidants. This is the first indication that LMWHA can act as a DAMP in keratinocytes. In conclusion LMWHA fragments are important mediators in the process of contact sensitisation leading to IL-18 dependent responses
Contact allergen (PPD and DNCB)-induced keratinocyte sensitization is partly mediated through a low molecular weight hyaluronan (LMWHA)/TLR4/NF-κB signaling axis
No full textAllergic contact dermatitis (ACD) is caused by topical exposure to chemical allergens. Keratinocytes play a key role in innate immunity, as well as in ACD progression. The transmembrane Toll-like receptor 4 (TLR4), strongly implicated in skin inflammation, has the ability to bind Damage Associated Molecular Patterns (DAMPs), like Low Molecular Weight Hyaluronan (LMWHA). Previously, we had determined that p-phenylenediamine (PPD) and 2,4-dinitrochlorobenzene (DNCB) modulate keratinocyte HA deposition in a manner correlated to their sensitization. In the present study, we aimed to investigate putative co-operation of HA and TLR4 in the process of PPD and DNCB-induced keratinocyte activation. Contact sensitizers were shown to significantly increase the expression of Hyaluronan Synthases (HAS) and TLR4 in NCTC2544 human keratinocytes, as demonstrated by western blot and Real-Time PCR. These data, in correlation to earlier shown enhanced HA degradation suggest that the contact sensitizers facilitate HA turnover of keratinocytes and increase the release of pro-inflammatory, LMWHA fragments. Treatment with exogenous LMWHA enhanced TLR4, HAS levels and Nuclear factor-kappa beta (NF-κΒ) activation. PPD, DNCB and LMWHA-effects were shown to be partly executed through TLR4 downstream signaling as shown by Real-Time, western blot, siRNA and confocal microscopy approaches. Specifically, PPD and DNCB stimulated the activation of the TLR4 downstream mediator NF-κB. Therefore, the shown upregulation of TLR4 expression is suggested to further facilitate the release of endogenous, bioactive HA fragments and sustain keratinocyte activation. In conclusion, keratinocyte contact allergen-dependent sensitization is partly mediated through a LMWHA/TLR4/ NF-κB signaling axis
Chemical-induced contact allergy: from mechanistic understanding to risk prevention
No full textChemical allergens are small molecules able to form a sensitizing complex once they bound to proteins. One of the most frequent manifestations of chemical allergy is contact hypersensitivity, which can have serious impact on quality of life. Allergic contact dermatitis is a predominantly CD8 + T cell-mediated immune disease, resulting in erythema and eczema. Chemical allergy is of considerable importance to the toxicologist, who has the responsibility of identifying and characterizing the allergenic potential of chemicals, and estimating the risk they pose to human health. This review aimed at exploring the phenomena of chemical-induced contact allergy starting from a mechanistic understanding, immunoregulatory mechanisms, passing through the potency of contract allergen until the hazard identification, pointing out the in vitro models for assessing contact allergen-induced cell activation and the risk prevention
Collagen VI and hyaluronan: the common role in breast cancer
No full textCollagen VI and hyaluronan are widely distributed extracellular matrix macromolecules that play a crucial role in tissue development and are highly expressed in cancers. Both hyaluronan and collagen VI are upregulated in breast cancer, generating a microenvironment that promotes tumour progression and metastasis. A growing number of studies show that these two molecules are involved in inflammation and angiogenesis by recruiting macrophages and endothelial cells, respectively. Additionally, collagen VI induces epithelial-mesenchymal transition that is correlated to increased synthesis of hyaluronan in mammary cells. Hyaluronan has also a specific role in cellular functions that depends mainly on the size of the polymer, whereas the effect of collagen VI in tumour progression may be the result of the intact molecule or the C5 peptide of α3(VI) chain, known as endotrophin. Collectively, these findings strongly support the parallel role of these molecules in tumour progression and suggest that they may be used as prognostic factors for the breast cancer treatment
Glycosaminoglycans: key players in cancer cell biology and treatment
No full textGlycosaminoglycans are natural heteropolysaccharides that are present in every mammalian tissue. They are composed of repeating disaccharide units that consist of either sulfated or non-sulfated monosaccharides. Their molecular size and the sulfation type vary depending on the tissue, and their state either as part of proteoglycan or as free chains. In this regard, glycosami-noglycans play important roles in physiological and pathological conditions. During recent years, cell biology studies have revealed that glycosaminoglycans are among the key macromolecules that affect cell properties and functions, acting directly on cell receptors or via interactions with growth factors. The accumulated knowledge regarding the altered structure of glycosaminoglycans in several diseases indicates their importance as biomarkers for disease diagnosis and progression, as well as pharmacological targets. This review summarizes how the fine structural characteristics of glycosaminoglycans, and enzymes involved in their biosynthesis and degradation, are involved in cell signaling, cell function and cancer progression. Prospects for glycosaminoglycan-based therapeutic targeting in cancer are also discussed
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