Transforming growth factor-beta (TGF-β) and oxidative stress/Reactive Oxygen Species (ROS) both have pivotal roles in health and disease. In this review we are analyzing the interplay between TGF-β and ROS in tumorigenesis and cancer progression. They have contradictory roles in cancer progression since both can have antitumor effects, through the induction of cell death, senescence and cell cycle arrest, and protumor effects by contributing to cancer cell spreading, proliferation, survival, and metastasis. TGF-β can control ROS production directly or by downregulating antioxidative systems. Meanwhile, ROS can influence TGF-β signaling and increase its expression as well as its activation from the latent complex. This way, both are building a strong interplay which can be taken as an advantage by cancer cells in order to increment their malignancy. In addition, both TGF-β and ROS are able to induce cell senescence, which in one way protects damaged cells from neoplastic transformation but also may collaborate in cancer progression. The mutual collaboration of TGF-β and ROS in tumorigenesis is highly complex, and, due to their differential roles in tumor progression, careful consideration should be taken when thinking of combinatorial targeting in cancer therapies.

located between cementum and alveolar bone has important role in regeneration of periodontal tissues damaged by mechanical or biochemical factors (Ozer et al., 2013). In order to maintain PDL homeostasis in both normal and pathologic conditions, resident PDL multipotent progenitors, or stem cell-like cells (PDLSCs) act depending on local tissue demands, since PDLSCs can differentiate into major cellular constituents of PDL, such are osteoblast, fibroblast, and cementoblasts, thus maintaining PDL structure and function (Bassir et al., 2016;Han, Menicanin, Gronthos, & Bartold, 2014;Liu et al., 2015;Mao, Robey, & Prockop, 2012;Zhu & Liang, 2015).Oral cavity presents host niche for pathogenic bacteria which may provoke host tissue inflammation, damage dental tissues homeostasis, and finally lead to gingivitis or periodontitis (Chatzivasileiou, Kriebel, Steinhoff, Kreikemeyer, & Lang, 2015), as well as various systemic diseases (Nagpal, Yamashiro, & Izumi, 2015;Seymour, Ford, Cullinan, Leishman, & Yamazaki, 2007 bovine serum (FBS; Capricorn-Scientific, Germany), 100 U/ml penicillin and 100 μg/ml streptomycin (Gibco, Thermo Fisher Scientific), and incubated at 37°C in humidified atmosphere containing 5% CO 2 (standard conditions). The medium was replaced twice a week, and after reaching the 90% of confluence, the cells were detached using 0.25% solution of trypsin/EDTA (Gibco). All experiments were performed using PDLSCs between passage two and six.Human peripheral blood mononuclear cells (MNCs) were isolated from fresh heparinized blood collected from 15 healthy voluntary unrelated donors by density gradient using lymphocyte separation medium Lymphocyte Separation Medium 1.077 g/ml (CapricornScientific). Purified MNCs were cultivated in RPMI-1640 medium (Sigma-Aldrich) supplemented with 10% FBS, 2 mM L-glutamine, 1 mM sodium pyruvate, 100 U/ml penicillin, and 100 μg/ml streptomycin in standard conditions.Human endothelial cell line (EA.hy926) was purchased from The American Type Culture Collection (ATCC, CRL-2922), MD, and cultured in GM in standard conditions. antibodies (Thermo Scientific) and CD14 (Sigma-Aldrich). The percentage of nonspecific binding was determined by using the appropriate FITC-and PE-conjugated isotype control antibodies (R&D Systems). Flow cytometry was performed using flow cytometer Cytomics FC 500 (Beckman Coulter). | Phenotype analysis | Multilineage differentiationFor evaluation of multilineage differentiation capacity PDLSCs were cultivated in GM or corresponding differentiation medium (DM) with orwithout LPS (1000 ng/ml, purchased from Sigma-Aldrich) in standard conditions. Osteogenic DM contained DMEM supplemented with 5% FBS, 100 U/ml penicillin/streptomycin, 50 µM ascorbic acid-2-phosphate (Sigma-Aldrich), and 10 mM β-glycerophosphate (SigmaAldrich). For osteogenic differentiation detection, alkaline phosphatase (ALP) staining has been followed after 7 days of cultivation, while calcium in DMEM, 100 U/ml penicilin/streptomycin, 100 µg/ml isobutylmethylxanthine (IBMX; Sigma-Aldrich),...

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The results obtained demonstrated that both MSCs represent good alternative sources of adult MSCs that could be used in cell therapy applications.

The present study evaluated the role of interleukin (IL) 17 in multilineage commitment of C2C12 myoblastic cells and investigated associated signaling pathways. The results concerning the effects on cell function showed that IL-17 inhibits the migration of C2C12 cells, while not affecting their proliferation. The data regarding the influence on differentiation demonstrated that IL-17 inhibits myogenic differentiation of C2C12 cells by down-regulating the myogenin mRNA level, myosin heavy chain expression and myotube formation, but promotes their osteogenic differentiation by up-regulating the Runt-related transcription factor 2 mRNA level, cyclooxygenase-2 expression and alkaline phosphatase activity. IL-17 exerted these effects by activating ERK1,2 mitogen activated protein kinase signaling pathway, which in turn regulated the expression of relevant genes and proteins to inhibit myogenic differentiation and induce osteogenic differentiation. Additional analysis showed that the induction of osteogenic differentiation by IL-17 is independent of BMP signaling. The results obtained demonstrate the potential of IL-17 not only to inhibit the myogenic differentiation of C2C12 myoblasts but also to convert their differentiation pathway into that of osteoblast lineage providing new insight into the capacities of IL-17 to modulate the differentiation commitment.

Mesenchymal stem cells from human adipose tissue (hASCs) are proposed as suitable tools for soft tissue engineering and reconstruction. Although it is known that hASCs have the ability to home to sites of inflammation and tumor niche, the role of inflammatory cytokines in the hASCs-affected tumor development is not understood. We found that interferon-c (IFN-c) and/or tumor necrosis factor-a (TNF-a) prime hASCs to produce soluble factors which enhance MCF-7 cell line malignancy in vitro. IFN-c and/or TNF-a-primed hASCs produced conditioned media (CM) which induced epithelial to mesenchymal transition (EMT) of MCF-7 cells by reducing E-Cadherin and increasing Vimentin expression. Induced EMT was accompanied by increased invasion, migration, and urokinase type-plasminogen activator (uPA) expression in MCF-7 cells. These effects were mediated by increased expression of transforming growth factor-b1(TGF-b1) in cytokines-primed hASCs, since inhibition of type I TGF-b1 receptor on MCF-7 cells and neutralization of TGF-b1 disabled the CM from primed hASCs to increase EMT, cell migration, and uPA expression in MCF-7 cells. Obtained data suggested that IFNc and/or TNF-a primed hASCs might enhance the malignancy of MCF-7 cell line by inducing EMT, cell motility and uPA expression in these cells via TGF-b1-Smad3 signalization, with potentially important implications in breast cancer progression.

Mesenchymal stem cells (MSCs) have the potential to migrate toward damaged tissues increasing tissue regeneration. Interleukin-17 (IL-17) is a proinflammatory cytokine with pleiotropic effects associated with many inflammatory diseases. Although IL-17 can modulate MSC functions, its capacity to regulate MSC migration is not well elucidated so far. Here, we studied the role of IL-17 on peripheral blood (PB) derived MSC migration and transmigration across endothelial cells. IL-17 increased PB-MSC migration in a wound healing assay as well as cell mobilization from collagen gel. Concomitantly IL-17 induced the expression of urokinase type plasminogen activator (uPA) without affecting matrix metalloproteinase expression. The incremented uPA expression mediated the capacity of IL-17 to enhance PB-MSC migration in a ERK1,2 MAPK dependent way. Also, IL-17 induced PB-MSC migration alongside with changes in cell polarization and uPA localization in cell protrusions. Moreover, IL-17 increased PB-MSC adhesion to endothelial cells and transendothelial migration, as well as increased the capacity of PB-MSC adhesion to fibronectin, in an uPA-dependent fashion. Therefore, our data suggested that IL-17 may act as chemotropic factor for PB-MSCs by incrementing cell motility and uPA expression during inflammation development.