The endothelial-to-mesenchymal transition changes the focal adhesion site proteins levels and the SLRP-lumican level in HMEC-1 cell line.

Scleroderma, the chronic autoimmune disease is a consequence of inflammation in the connective tissue. Prolonged duration affects formation of compact connective tissue strands (scarring) within the target organ. Endothelial cells undergoing endothelial-to-mesenchymal transition (EndMT) are the source of fibroblast phenotype-resembling cells.

Arabinoxylan-Based Microcapsules Being Loaded with Bee Products as Bioactive Food Components Are Able to Modulate the Cell Migration and Inflammatory Response-In Vitro Study.

The aim of the research was to use bioactive heteropolysaccharides isolated from rye bran to obtain innovative systems for the controlled release of bioactive compounds. The core of the obtained encapsulates was honey and royal jelly. It was shown for the first time that preparations effectively ameliorated inflammatory response in lipopolysaccharide (LPS)-treated RAW 264.

Oxidative Stress Enhances the TGF-β2-RhoA-MRTF-A/B Axis in Cells Entering Endothelial-Mesenchymal Transition.

Around 45% of deaths in the EU and the US are due to fibrotic diseases. Although myofibroblasts are detected in various fibrotic tissues, they are mostly transdifferentiated from endothelial cells during the endothelial-mesenchymal transition (EndMT) induced by tumor growth factor-beta (TGF-β) family members. Growing evidence indicates that oxidative stress might enhance the sensitivity and the effects of TGF-β stimulation; however, the molecular mechanisms involved in the coordination of oxidative stress and TGF-β inductions remain poorly understood.

The New Model of Snail Expression Regulation: The Role of MRTFs in Fast and Slow Endothelial-Mesenchymal Transition.

Endothelial-mesenchymal transition (EndMT) is a crucial phenomenon in regulating the development of diseases, including cancer metastasis and fibrotic disorders. The primary regulators of disease development are zinc-finger transcription factors belonging to the Snail family. In this study, we characterized the myocardin-related transcription factor (MRTF)-dependent mechanisms of a human promoter regulation in TGF-β-stimulated human endothelial cells.

Endothelial Cells in the Tumor Microenvironment.

Angiogenesis is a critical process required for tumor progression. Newly formed blood vessels provide nutrition and oxygen to the tumor contributing to its growth and development. However, endothelium also plays other functions that promote tumor metastasis.

Transforming Growth Factor-β Receptor Internalization via Caveolae Is Regulated by Tubulin-β2 and Tubulin-β3 during Endothelial-Mesenchymal Transition.

Fibrotic disorders, which are caused by long-term inflammation, are observed in numerous organs. These disorders are regulated mainly through transforming growth factor (TGF)-β family proteins by a fundamental cellular mechanism, known as the endothelial-mesenchymal transition. Therefore, there is a pressing need to identify the mechanisms and potential therapeutic targets that enable the inhibition of endothelial transdifferentiation.

TUBB4B Downregulation Is Critical for Increasing Migration of Metastatic Colon Cancer Cells.

Tumor metastasis, the major problem for clinical oncology in colon cancer treatment, is linked with an epithelial-mesenchymal transition (EMT). The observed cellular transformation in this process is manifested by cell elongation, enhanced cell migration and invasion ability, coordinated by cytoskeleton reorganization. In the present study, we examined the role of tubulin-β4 (TUBB4B) downregulation that occurs during EMT in colon cancer cells, in the modulation of the function of microtubules.

Nonsteroidal Anti-Inflammatory Drugs Prevent Vincristine-Dependent Cancer-Associated Fibroblasts Formation.

Vincristine is used in the clinical treatment of colon cancer, especially in patients diagnosed in the advanced phase of cancer development. Unfortunately, similar to other agents used during antitumor therapy, vincristine might induce chemoresistance. Studies of this process focus mainly on the analysis of the molecular mechanisms within cancer, usually ignoring the role of stromal cells.

Invasive Colon Cancer Cells Induce Transdifferentiation of Endothelium to Cancer-Associated Fibroblasts through Microtubules Enriched in Tubulin-β3.

Colon cancer, the second leading cause of cancer-related deaths in the world, is usually diagnosed in invasive stages. The interactions between cancer cells and cells located in their niche remain the crucial mechanism inducing tumor metastasis. The most important among those cells are cancer-associated fibroblasts (CAFs), the heterogeneous group of myofibroblasts transdifferentiated from numerous cells of different origin, including endothelium.

The ILK-MMP9-MRTF axis is crucial for EndMT differentiation of endothelial cells in a tumor microenvironment.

Increasing evidence indicates that the tumor microenvironment is a critical factor supporting cancer progression, chemoresistance and metastasis. Recently, cancer-associated fibroblasts (CAFs) have been recognized as a crucial tumor stromal component promoting cancer growth and invasiveness via modulation of the extracellular matrix (ECM) structure, tumor metabolism and immune reprogramming. One of the main sources of CAFs are endothelial cells undergoing the endothelial-mesenchymal transition (EndMT).

Filamin A upregulation correlates with Snail-induced epithelial to mesenchymal transition (EMT) and cell adhesion but its inhibition increases the migration of colon adenocarcinoma HT29 cells.

Filamin A (FLNA) is actin filament cross-linking protein involved in cancer progression. Its importance in regulating cell motility is directly related to the epithelial to mesenchymal transition (EMT) of tumor cells. However, little is known about the mechanism of action of FLNA at this early stage of cancer invasion.

Tubulin beta 3 and 4 are involved in the generation of early fibrotic stages.

The endothelial-mesenchymal transition (EndMT) is a fundamental cellular mechanism that occurs under both physiological and pathological conditions and includes the fibrotic stages of numerous organs, namely, the skin, kidneys, heart, lungs and liver. Endothelial cells that undergo EndMT are one of the main source of (myo)fibroblasts in fibrotic tissues. A critical step in cellular transdifferentiation is morphological change, which is engineered by the reorganization of cytoskeletal elements such as microtubules.

Senescent endothelial cells: Potential modulators of immunosenescence and ageing.

Recent studies have demonstrated that the accumulation of senescent endothelial cells may be the primary cause of cardiovascular diseases. Because of their multifunctional properties, endothelial cells actively take part in stimulating the immune system and inflammation. In addition, ageing is characterized by the progressive deterioration of immune cells and a decline in the activation of the immune response.

β-III tubulin modulates the behavior of Snail overexpressed during the epithelial-to-mesenchymal transition in colon cancer cells.

Class III β-tubulin (TUBB3) is a marker of drug resistance expressed in a variety of solid tumors. Originally, it was described as an important element of chemoresistance to taxanes. Recent studies have revealed that TUBB3 is also involved in an adaptive response to a microenvironmental stressor, e.

[MRTFs protein family and its role in pathological stages].

The MRTFs (myocardin-releated transcription factors) protein family consists of myocardin, MRTF-A (MKL1, MAL) and MRTF-B (MKL2). These proteins are included in the common family due to the presence of evolutionarily conserved domains which are responsible for homo- and heterodimerization with other members of the family as well as actin binding and transcription activation. Despite high structural homology, these factors present different characteristics in terms of localization.

[Filamin A as a mediator of alterations in cancer cells].

Filamin A (FLNA, filamin-1) is a homodimeric protein, commonly expressed in animal organisms. Its basic function in the cell is actin crosslinking and forming 3D cytoskeleton structure. Filamin-1 interacts with more than 60 different proteins with various functions such as: cell membrane and cytoskeleton formation, maintaining cell shape, intracellular signaling, nuclear functions or GTP-binding proteins regulation.

Downregulation of microsomal glutathione-S-transferase 1 modulates protective mechanisms in differentiated PC12 cells.

Microsomal glutathione-S-transferase 1 (Mgst1) plays a specific role in protection of cells against oxidative stress. In this study, we assayed the effect of Mgst1 downregulation on cells behavior using differentiated PC12 line, a widely accepted neuronal model system. We have developed stable transfected cells with downregulated Mgst1 (PC12_M), which were differentiated with 1 mM dibutyryl-cAMP (db-cAMP).

Distinct inhibitory efficiency of siRNAs and DNAzymes to β1 integrin subunit in blocking tumor growth.

Receptors of the β1 integrin family are involved in many tumor-promoting activities. There are several approaches currently used to control integrin activity, and thus to potentially restrain tumor metastasis and angiogenesis. In this study, we compared inhibitory efficiencies of siRNA and DNAzymes against the β1 integrin subunit (DEβ1), in a mouse xenograft model.

Effect of lumican on the migration of human mesenchymal stem cells and endothelial progenitor cells: involvement of matrix metalloproteinase-14.

Background: Increasing number of evidence shows that soluble factors and extracellular matrix (ECM) components provide an optimal microenvironment controlling human bone marrow mesenchymal stem cell (MSC) functions. Successful in vivo administration of stem cells lies in their ability to migrate through ECM barriers and to differentiate along tissue-specific lineages, including endothelium. Lumican, a protein of the small leucine-rich proteoglycan (SLRP) family, was shown to impede cell migration and angiogenesis.

[Cancer stem cells].

Cancer stem cell theory gains increasingly greater significance in the world of medicine. Numerous findings of scientific research in vivo and in vitro indicate that it is the population of undifferentiated, self-renewing cells which is responsible for recurrence of cancer and metastasis. Similarly to normal stem cells, cancer stem cells (CSC) function in the environment of the other cells of the organism, called the niche, where they receive signals for differentiation and proliferation processes.

Downregulation of PMCA2 or PMCA3 reorganizes Ca(2+) handling systems in differentiating PC12 cells.

Changes in PMCA2 and PMCA3 expression during neuronal development are tightly linked to structural and functional modifications in Ca(2+) handling machinery. Using antisense strategy we obtained stably transfected PC12 lines with reduced level of PMCA2 or PMCA3, which were then subjected to dibutyryl-cAMP differentiation. Reduced level of neuron-specific PMCAs led to acceleration of differentiation and formation of longer neurites than in control PC12 line.

Lumican inhibits angiogenesis by interfering with α2β1 receptor activity and downregulating MMP-14 expression.

Introduction: Previous studies showed that lumican, a small leucine-rich proteoglycan that binds to α2 integrin I domain, is an efficient inhibitor of cell adhesion and migration. In this report, we tested its effect on angiogenesis in vitro and in vivo.

Materials And Methods: Effect of lumican on angiogenesis was evaluated by in vitro capillary tube formation test performed between Fibrin II Gels or in Matrigel™ and in vivo by Matrigel(™) plug assay in BALB/c mice.

Functional characteristic of PC12 cells with reduced microsomal glutathione transferase 1.

Microsomal glutathione transferase 1 (MGST1) possesses glutathione transferase and peroxidase activities and is active in biotransformation of xenobiotics and in defense against oxidative stress. To assess MGST1 role in the development and functioning of PC12 cells, we constructed a cell line with reduced MGST1 (PC12_M). Real-time PCR and immunoblot assays showed MGST1 expression lowered to 60 % and immunocytochemical analyses demonstrated an altered concentration and distribution of the enzyme.

DNAzyme as an efficient tool to modulate invasiveness of human carcinoma cells.

In this study we evaluated efficiency of DNAzymes to modulate motility of cancer cells, an important factor in the progression and metastasis of cancers. For this purpose we targeted β1 integrins that are predominant adhesive receptors in various carcinoma cell lines (CX1.1, HT29, LOVO, LS180, PC-3).

Thymosin beta4 regulates migration of colon cancer cells by a pathway involving interaction with Ku80.

Aberrant expression of thymosin beta4 (Tbeta4) has recently been found to be associated with colorectal carcinoma (CRC) progression evidently due to an increase of the motility and invasion of tumor cells and the induction of a proangiogenic phenotype of endothelial cells. Both mechanisms depend upon matrix-degrading proteases, particularly plasmin and matrix metalloproteinases (MMPs) that are responsible for extensive tissue remodeling. Cleavage of ECM macromolecules weakens the structural integrity of tissues and exposes cryptic domains of extracellular components, which elicit biological responses distinct from intact molecules.