Steviol glycosides affect functional properties and macromolecular expression of breast cancer cells.

Steviol glycosides, the active sweet components of stevia plant, have been recently found to possess a number of therapeutic properties, including some recorded anticancer ones against various cancer cell types (breast, ovarian, cervical, pancreatic, and colon cancer). Our aim was to investigate this anticancer potential on the two most commonly used breast cancer cell lines which differ in the phenotype and estrogen receptor (ER) status: the low metastatic, ERα+ MCF-7 and the highly metastatic, ERα-/ERβ+ MDA-MB-231. Specifically, glycosides' effect was studied on cancer cells': (a) viability, (b) functionality (proliferation, migration, and adhesion), and (c) gene expression (mRNA level) of crucial molecules implicated in cancer's pathophysiology.

A guide to the composition and functions of the extracellular matrix.

Extracellular matrix (ECM) is a dynamic 3-dimensional network of macromolecules that provides structural support for the cells and tissues. Accumulated knowledge clearly demonstrated over the last decade that ECM plays key regulatory roles since it orchestrates cell signaling, functions, properties and morphology. Extracellularly secreted as well as cell-bound factors are among the major members of the ECM family.

Evaluation of lumican effects on morphology of invading breast cancer cells, expression of integrins and downstream signaling.

The small leucine-rich proteoglycan lumican regulates estrogen receptors (ERs)-associated functional properties of breast cancer cells, expression of matrix macromolecules, and epithelial-to-mesenchymal transition. However, it is not known whether the ER-dependent lumican effects on breast cancer cells are related to the expression of integrins and their intracellular signaling pathways. Here, we analyzed the effects of lumican in three breast cancer cell lines: the highly metastatic ERβ-positive MDA-MB-231, cells with the respective ERβ-suppressed (shERβMDA-MB-231), and lowly invasive ERα-positive MCF-7/c breast cancer cells.

A guide to hyaluronan and related enzymes in breast cancer: biological significance and diagnostic value.

Hyaluronan (HA) is a unique nonsulfated glycosaminoglycan that contributes to breast cancer cells growth and functional properties, including cell migration, invasion, adhesion, as well as tumor-associated angiogenesis in different stages of breast cancer progression and especially metastasis. Latest data show that the levels of HA and/or low molecular mass HA in blood serum and plasma of breast cancer patients may be a useful biomarker for breast cancer prognosis, differential diagnosis, and patients' treatment monitoring. Therefore, the qualitative and quantitative determination of HA in biological samples is an emerging area of research.

Analyzing Hyaluronidases in Biological Fluids.

Hyaluronidases are a group of enzymes responsible for the degradation of hyaluronan. They seem to be associated with a plethora of pathological conditions, as it has been showcased by numerous studies over the past years. The emerging role of hyaluronidases in various pathological states, especially cancer, is of a great interest.

Tumor-suppressive functions of 4-MU on breast cancer cells of different ER status: Regulation of hyaluronan/HAS2/CD44 and specific matrix effectors.

The malignant phenotype of various cancers is linked to enhanced expression of hyaluronan, a pro-angiogenic glycosaminoglycan whose expression is suppressed by 4-methylumbelliferone (4-MU), a non-toxic oral agent used as a dietary supplement to improve health and combat prostate cancer. In this study, we investigated the role of 4-MU in mammary carcinoma cells with distinct malignant phenotypes and estrogen receptor (ER) status, a major prognostic factor in the clinical management of breast cancers. We focused on two breast cancer cell lines, the low metastatic and ERα+ MCF-7 cells, and the highly-aggressive and ERα- MDA-MB-231 cells.

Lumican effectively regulates the estrogen receptors-associated functional properties of breast cancer cells, expression of matrix effectors and epithelial-to-mesenchymal transition.

Lumican is a small leucine-rich proteoglycan that has been shown to contribute in several physiological processes, but also to exert anticancer activity. On the other hand, it has been recently shown that knockdown of the estrogen receptor α (ERα) in low invasive MCF-7 (ERα+) breast cancer cells and the suppression of ERβ in highly aggressive MDA-MB-231 (ERβ+) cells significantly alter the functional properties of breast cancer cells and the gene expression profile of matrix macromolecules related to cancer progression and cell morphology. In this report, we evaluated the effects of lumican in respect to the ERs-associated breast cancer cell behaviour, before and after suppression of ERs, using scanning electron and confocal microscopies, qPCR and functional assays.

The role of heparins and nano-heparins as therapeutic tool in breast cancer.

Glycosaminoglycans are integral part of the dynamic extracellular matrix (ECM) network that control crucial biochemical and biomechanical signals required for tissue morphogenesis, differentiation, homeostasis and cancer development. Breast cancer cells communicate with stromal ones to modulate ECM mainly through release of soluble effectors during cancer progression. The intracellular cross-talk between cell surface receptors and estrogen receptors is important for the regulation of breast cancer cell properties and production of ECM molecules.

Emerging aspects of nanotoxicology in health and disease: From agriculture and food sector to cancer therapeutics.

Nanotechnology is an evolving scientific field that has allowed the manufacturing of materials with novel physicochemical and biological properties, offering a wide spectrum of potential applications. Properties of nanoparticles that contribute to their usefulness include their markedly increased surface area in relation to mass, surface reactivity and insolubility, ability to agglomerate or change size in different media and enhanced endurance over conventional-scale substance. Here, we review nanoparticle classification and their emerging applications in several fields; from active food packaging to drug delivery and cancer research.

ADAMTS expression in colorectal cancer.

ADAMTSs are a family of secreted proteinases that share the metalloproteinase domain with matrix metalloproteinases (MMPs). By acting on a large panel of extracellular substrates, they control several cell functions such as fusion, adhesion, proliferation and migration. Through their thrombospondin motifs they also possess anti-angiogenic properties.

Metabolism of cartilage proteoglycans in health and disease.

Cartilage proteoglycans are extracellular macromolecules with complex structure, composed of a core protein onto which a variable number of glycosaminoglycan chains are attached. Their biosynthesis at the glycosaminoglycan level involves a great number of sugar transferases well-orchestrated in Golgi apparatus. Similarly, their degradation, either extracellular or intracellular in lysosomes, involves a large number of hydrolases.

Syndecans as modulators and potential pharmacological targets in cancer progression.

Extracellular matrix (ECM) components form a dynamic network of key importance for cell function and properties. Key macromolecules in this interplay are syndecans (SDCs), a family of transmembrane heparan sulfate proteoglycans (HSPGs). Specifically, heparan sulfate (HS) chains with their different sulfation pattern have the ability to interact with growth factors and their receptors in tumor microenvironment, promoting the activation of different signaling cascades that regulate tumor cell behavior.

Biomechanical and structural changes following the decellularization of bovine pericardial tissues for use as a tissue engineering scaffold.

To achieve natural scaffolds for tissue engineering applications we decellularized bovine pericardial (BP) tissues according to two different protocols: a novel treatment based on Triton(®) X-100 (12 h, 4 °C) (BP1) and a trypsin/EDTA treatment (37 °C, 48 h) (BP2). Results were compared with commercially available acellular xenogeneic biomaterials, Veritas(®) and Collamed(®). Biomechanical characteristics, high (E(h)) and low (E(l)) modulus of elasticity, of the fresh untreated tissue varied with the anatomical direction (apex to base (T) to transverse (L)) (mean ± SDEV): (41.

Chondroitin synthases I, II, III and chondroitin sulfate glucuronyltransferase expression in colorectal cancer.

Glycosaminoglycans undergo significant structural alterations in cancer, namely in terms of their sulfation pattern and hydrodynamic size. Numerous studies have focused on this issue, and have demonstrated that glycosaminoglycans play a crucial role in cancer growth and invasion. However, the majority of the enzymes involved in glycosaminoglycan alterations have yet to be examined in detail.

The chondroitin/dermatan sulfate synthesizing and modifying enzymes in laryngeal cancer: expressional and epigenetic studies.

Background: Significant biochemical changes are observed in glycosaminoglycans in squamous cell laryngeal carcinoma. The most characteristics are in chondroitin/dermatan sulfate fine structure and proportion, which might be due to differential expression of the enzymes involved in their biosynthesis. The aim of the present work was the investigation in expressional and epigenetic level of the enzymes involved in chondroitin/dermatan sulfate biosynthesis in laryngeal cancer.

Involvement of hyaluronidases in colorectal cancer.

Background: Hyaluronidases belong to a class of enzymes that degrade, predominantly, hyaluronan. These enzymes are known to be involved in physiological and pathological processes, such as tumor growth, infiltration and angiogenesis, but their exact role in tumor promotion or suppression is not clear yet. Advanced colorectal cancer is associated with elevated amounts of hyaluronan of varying size.

Alterations of glycosaminoglycan disaccharide content and composition in colorectal cancer: structural and expressional studies.

The glycosaminoglycans are implicated in many processes important in the growth and progression of malignant tumors. In the present study glycosaminoglycans were purified from healthy, macroscopically normal and cancerous specimens of different anatomic sites and different stages of cancer and analyzed by FACE after chondroitinases and sulfatases digestion. The cancerous samples contained increased levels of 6-sulfated unsaturated disaccharides compared to macroscopically normal and healthy samples, the increase being stage-related.

Keratan sulfate-containing proteoglycans in sheep brain with particular reference to phosphacan and synaptic vesicle proteoglycan isoforms.

Proteoglycans (PGs) are widely expressed in all areas of the brain. In this study, the keratan sulfate-containing PGs (KS-PGs) from cerebrum (CB), cerebellum (CL) and brainstem (BS) of young sheep brain were isolated, purified and characterized. The amount of KS-PGs in CL was significantly lower than that in CB and BS.

Biochemical changes of extracellular proteoglycans in squamous cell laryngeal carcinoma.

Larynx is a complicated organ with peculiar properties, having a noticeable impact in vocal and respiratory physiology. In squamous cell laryngeal carcinoma, the extracellular matrix components underwent significant modifications concerning their fine chemical structure. Degradation of aggrecan is observed, whereas versican and decorin amounts are increased.

The structural and compositional changes of glycosaminoglycans are closely associated with tissue type in human laryngeal cancer.

Hyaluronan and sulfated glycosaminoglycans, as intrinsic components of proteoglycans, are playing important roles in cancer biology. In the present study, we investigated in detail the glycosaminoglycans on both fine chemical and structural levels in laryngeal cartilaginous and non-cartilaginous tissues at different stages of laryngeal cancer. The results indicated that in cartilaginous tissues the amounts of chondroitin sulfate, keratan sulfate, dermatan sulfate and hyaluronan presented a dramatic decrease in contrast to the non-cartilaginous tissues, which showed a significant increase of these glycosaminoglycans compared to their normal counterparts.

Cartilage aggrecan undergoes significant compositional and structural alterations during laryngeal cancer.

Aggrecan is a key component of cartilage and is responsible for the integrity and function of the tissue. In this study, the content of aggrecan and its structural modifications in adjacent to cancer apparently normal cartilages (AANCs) from various stages of laryngeal squamous cell carcinoma (LSCC) were investigated. Our data demonstrated a stage-related loss of aggregable aggrecan in AANCs, compared to the healthy laryngeal cartilage (HLC), which was excessive in advanced stages of disease.

Preparation of cross-linked cellulases and their application for the enzymatic production of glucose from municipal paper wastes.

Hydrolysis of cellulosic wastes has been applied for environmental purposes and glucose production. An enzymatic process is proposed for such treatment of municipal cellulosic wastes, and the optimum conditions are described. It was found that different conditions should be applied for the treatment of soft or hard paper wastes, the most characteristic being pretreatment of wastes and temperature of the treatment process.

The extractability of extracellular matrix components as a marker of cartilage remodeling in laryngeal squamous cell carcinoma.

Sequential extraction was applied to investigate the proteoglycan (PG) organization in healthy laryngeal cartilage (HLC) and laryngeal cartilage squamous cell carcinoma (LCSCC). Highly stable aggrecan aggregates, extracted from both HLC and LCSCC with strong dissociative reagents, i.e.

Changes of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in the serum of patients with autoimmune diseases: association with age and disease activity.

Matrix metalloproteinases participate in the degradation of the extracellular matrix proteins and are regulated mainly by their respective tissue inhibitors. In a variety of inflammatory connective tissue diseases, variations in the tissue content of both metalloproteinases and tissue inhibitors have been reported. The purpose of this study was to determine the serum levels of metalloproteinases and tissue inhibitors in patients with autoimmune diseases and compare with those of healthy individuals of similar age.

Matrix proteoglycans are markedly affected in advanced laryngeal squamous cell carcinoma.

Proteoglycans (PGs) are implicated in the growth and progression of malignant tumors. In this study, we examined the concentration and localization of PGs in advanced (stage IV) laryngeal squamous cell carcinoma (LSCC) and compared with human normal larynx (HNL). LSCC and HNL sections were examined immunohistochemically with a panel of antibodies, and tissues extracts were analyzed by biochemical methods including immunoblotting and high performance liquid chromatography (HPLC).