Regulation of mucin expression: mechanistic aspects and implications for cancer and inflammatory diseases.

Neoplastic lesions typically express specific carbohydrate antigens on glycolipids, mucins, and other glycoproteins. Such antigens are often under epigenetic control and are subject to reversion and loss upon therapeutic selective pressure. We report here that two of the most common tumor-associated carbohydrate antigens, Tn and sialyl Tn (STn), result from somatic mutations in the gene Cosmc that encodes a molecular chaperone required for formation of the active T-synthase. Diverse neoplastic lesions, including colon cancer and melanoma-derived cells lines, expressed both Tn and STn antigen due to loss-of-function mutations in Cosmc. In addition, two human cervical cancer specimens that showed expression of the Tn/STn antigens were also found to have mutations in Cosmc and loss of heterozygosity for the cross-linked Cosmc locus. This is the first example of somatic mutations in multiple types of cancers that cause global alterations in cell surface carbohydrate antigen expression.

https://cancerres.aacrjournals.org/content/canres/68/6/1636.full.pdf

Human Tumor Antigens Tn and Sialyl Tn Arise from Mutations in Cosmc

Glycosylation changes that occur in cancer often lead to the expression of tumour-associated carbohydrate antigens. In breast cancer, these antigens are usually associated with a poor prognosis and a reduced overall survival. Cellular models have shown the implication of these antigens in cell adhesion, migration, proliferation and tumour growth. The present review summarizes our current knowledge of glycosylation changes (structures, biosynthesis and occurrence) in breast cancer cell lines and primary tumours, and the consequences on disease progression and aggressiveness. The therapeutic strategies attempted to target tumour-associated carbohydrate antigens in breast cancer are also discussed.

/pdf/tumour-associated-carbohydrate-antigens-in-breast-cancer-3g3g3xcylt.pdf

Tumour-associated carbohydrate antigens in breast cancer

Germin and germin-like proteins (GLPs) are encoded by a family of genes found in all plants. They are part of the cupin superfamily of biochemically diverse proteins, a superfamily that has a conserved tertiary structure, though with limited similarity in primary sequence. The subgroups of GLPs have different enzyme functions that include the two hydrogen peroxide-generating enzymes, oxalate oxidase (OxO) and superoxide dismutase. This review summarizes the sequence and structural details of GLPs and also discusses their evolutionary progression, particularly their amplification in gene number during the evolution of the land plants. In terms of function, the GLPs are known to be differentially expressed during specific periods of plant growth and development, a pattern of evolutionary subfunctionalization. They are also implicated in the response of plants to biotic (viruses, bacteria, mycorrhizae, fungi, insects, nematodes, and parasitic plants) and abiotic (salt, heat/cold, drought, nutrient, and metal) stress. Most detailed data come from studies of fungal pathogenesis in cereals. This involvement with the protection of plants from environmental stress of various types has led to numerous plant breeding studies that have found links between GLPs and QTLs for disease and stress resistance. In addition the OxO enzyme has considerable commercial significance, based principally on its use in the medical diagnosis of oxalate concentration in plasma and urine. Finally, this review provides information on the nutritional importance of these proteins in the human diet, as several members are known to be allergenic, a feature related to their thermal stability and evolutionary connection to the seed storage proteins, also members of the cupin superfamily.

/pdf/germin-and-germin-like-proteins-evolution-structure-and-3m2s90wi1l.pdf

Germin and Germin-like Proteins: Evolution, Structure, and Function

Mucins are the most abundant high molecular weight glycoproteins in mucus. Their nature and glycosylation content dictates the biochemical and biophysical properties of viscoelastic secretions, pointing out an important role in diverse biological functions, such as differentiation, cell adhesions, immune responses, and cell signaling. Mucins are expressed in tubular organs by specialized epithelial cells in the body. Their aberrant expression is well documented in a variety of inflammatory or malignant diseases. From a prognosis point of view, their expression and alterations in glycosylation are associated with the development and progression of malignant diseases. Therefore, mucins can be used as valuable markers to distinguish between normal and disease conditions. Indeed, this alteration in glycosylation patterns generates several epitopes in the oligosaccharide side chains that can be used as diagnostic and/or prognostic markers. Furthermore, these characteristic tumor-associated epitopes are extensively used as appropriate immunotargets of malignant epithelial cells. Therefore, in an effort to detect and treat cancer at the earliest stage possible, mucins are analyzed as potential markers of disease for diagnosis, progression, and for therapeutic purposes. In this review, we focused on the current status of the distribution of mucins in normal and pathologic conditions and their clinical use both in cancer diagnosis and therapeutics treatments.

/pdf/current-status-of-mucins-in-the-diagnosis-and-therapy-of-5c9nxlxcdz.pdf

Current status of mucins in the diagnosis and therapy of cancer

Background. Rheumatoid arthritis (RA), reactive arthritis (ReA), and osteoarthritis (OA) are a group of joint dis− eases which differ in pathogenesis, intensity, and rate of progression. They are characterized by different stages of irreversible damage to the extracellular matrix of the cartilage caused by enzymatic degradation. The aim was to compare the activities of elastase and gelatinase in synovial fluid (SF) samples from patients with reactive arthri− tis with those of patients with OA and RA and determine correlations between elastase activity and cartilage matrix degradation. Material and Methods. Elastase activity was determined using the low−molecular−weight synthetic substrate MeOSuc−Ala−Ala−Pro−Val−p−NA and gelatinolytic activity using zymography. The concentrations of collagen and proteoglycan degradation products were measured by spectrophotometric methods. Results. Elastase activity was detectable in 92% of the patients with ReA and RA and in 75% of those with OA. The elastase activity in SF samples from ReA patients, mainly due to metalloenzymatic activity, amounted to about 66% of this activity in RA patients and was 2.3−times higher than in the OA patients. Activation of prometallopro− teases resulted in a 4.5−fold increase in elastinolytic activity in ReA compared with a 3.2−fold increase in OA and a 4−fold increase in RA fluids. In contrast to OA, significant correlations between elastase activity and both gly− cosaminoglycans and type II collagen concentrations were found in SF samples of patients with ReA and RA. Furthermore, the active forms of two gelatinase proenzymes (92 and 72 kDa, respectively) were detected in ReA and RA synovial fluids. Conclusions. These results indicate that in ReA and RA, both elastase and gelatinases can contribute in similar degree to the degradation of major cartilage components (Adv Clin Exp Med 2008, 17, 5, 559–564).

Elastase and Gelatinase Activities in Synovial Fluid of Patients with Reactive Arthritis, Osteoarthritis, and Rheumatoid Arthritis

The gastric epithelial cells ribosome-UDP-GalNAc complex is a donor of UDP-GalNAc as the substrate for N-acetylgalactosaminyltransferase, which catalyse the transfer of GalNAc residue to the polypeptide, existing on polysomes. It was observed that the deglycosylated porcine mucin and synthetic peptide (PTSSPIST) can be also glycosylated with participation of N-acetylgalactosaminyltransferase and ribosome-UDP-GalNAc complex. The probability of the ribosome-UDP-GalNAc complex as an intermediate in the O-glycosylation is considered.

/pdf/the-participation-of-ribosome-udp-galnac-complex-in-the-2h41a0xhnd.pdf

The participation of ribosome-UDP-GalNAc complex in the initiation of protein glycosylation in vitro.

Elastase and Gelatinase Activities in Synovial Fluid of Patients with Reactive Arthritis, Osteoarthritis, and Rheumatoid Arthritis Aktywność elastazy i żelatynazy w płynie stawowym pacjentów z reaktywnym zapaleniem stawów, chorobą zwyrodnieniową i reumatoidalnym zapaleniem stawów

Halina Porowska

Papers

Elastase and Gelatinase Activities in Synovial Fluid of Patients with Reactive Arthritis, Osteoarthritis, and Rheumatoid Arthritis

The participation of ribosome-UDP-GalNAc complex in the initiation of protein glycosylation in vitro.

Elastase and Gelatinase Activities in Synovial Fluid of Patients with Reactive Arthritis, Osteoarthritis, and Rheumatoid Arthritis Aktywność elastazy i żelatynazy w płynie stawowym pacjentów z reaktywnym zapaleniem stawów, chorobą zwyrodnieniową i reumatoidalnym zapaleniem stawów