Abstract Mouse monoclonal antibodies have been raised against human milk‐fat globule membranes (HMFGM) to obtain reagents for mammary tumor diagnosis. A panel of 17 anti‐HMFGM was selected further investigation. Antibody‐blocking studies indicated that with these at least nine different non‐overlapping epitopes could be distinguished on six differend molecules, MAM‐1 MAM‐6. Electron microscopic the cellular localization antigens detected by some revealed they were present cell membrane...

Episialin (MUC1) is a transmembrane molecule with large mucin-like extracellular domain protruding high above the cell surface. The located at apical side of most glandular epithelial cells, whereas in carcinoma cells it often present entire surface and frequently expressed abnormally quantities. We have previously shown that overexpression episialin reduces cell-cell interactions. Here we show integrin-mediated adhesion to matrix transfectants melanoma line (A375), transformed (MDCK-ras-e)...

Episialin (MUC1, PEM, EMA, CA15-3 antigen) is a sialylated, membrane-associated glycoprotein with an extended mucin-like ectodomain. This domain mainly consists of 30-90 homologous 20-amino acid repeats that are rich in O-glycosylation sites (serines and threonines). It likely this part forms polyproline beta-turn helix. As result, the ectodomain can protrude more than 200 nm above cell surface, whereas most surface molecules do not exceed length 35 nm. Normally, episialin present at apical...

Episialin is a mucin-type glycoprotein present at the luminal side of most glandular epithelial cells. We have isolated cDNA clones encoding episialin and determined structure gene. The gene encodes transmembrane protein which consists of, for greater part, tandem repeats 20 amino acids. number these varies between 40 90 among different alleles. remainder are very rich in potential O-linked glycosylation sites. Two splice variants were found. Interestingly, proteins encoded by two differ...

Patients with metastatic cancer commonly have increased serum galectin-3 concentrations, but it is not known whether this has any functional implications for progression. We report that MUC1, a large transmembrane mucin protein overexpressed and aberrantly glycosylated in epithelial cancer, natural ligand galectin-3. Recombinant at concentrations (0.2-1.0 microg/ml) similar to those found the sera of patients adhesion MUC1-expressing human breast (ZR-75-1) colon (HT29-5F7) cells umbilical...

cDNA for the epithelial sialomucin episialin encodes a transmembrane molecule with large extracellular domain, which mainly consists of repeats 20 amino acids. Here we confirm existence previously proposed proteolytic cleavage that occurs in endoplasmic reticulum (Hilkens, J., and Buijs, F. (1988) J. Biol. Chem. 263, 4215-4222) show similar takes place vitro translation systems. Using truncated mRNAs, map site to region located between 71 53 acids upstream domain. Analysis mutant, this has...

Abstract Episialin (MUC1) is a mucin-like glycoprotein abundantly expressed on most carcinoma cells. As result of its extended and rigid structure, it reduces intercellular adhesion. We investigated whether this antiadhesion function allows tumor cells expressing high levels episialin to escape from immune recognition. To test hypothesis, we transfected episialin-negative (episialin-) melanoma (A375) with the MUC1 cDNA-encoding episialin. The results demonstrated that episialin-positive...

Formation of tumour cell aggregation/emboli prolongs the survival circulating cells in circulation, enhances their physical trapping micro-vasculature and thus increases metastatic spread cancer to remote sites.It shows here that presence galactoside-binding galectin-3, whose concentration is markedly increased blood circulation patients, homotypic aggregation under anchorage-independent conditions by interaction with oncofetal Thomsen-Friedenreich carbohydrate (Galbeta1,3GalNAcalpha-, TF)...

Abstract Adhesion of circulating tumor cells to the blood vessel endothelium is a critical step in cancer metastasis. We show this study that galectin-3, concentration which greatly increased circulation patients, increases cell adhesion macrovascular and microvascular endothelial under static flow conditions, transendothelial invasion, decreases latency experimental metastasis athymic mice. These effects galectin-3 are shown be consequence its interaction with cancer-associated MUC1, breaks...

The development of the mouse mammary gland was studied immunohistochemically using monoclonal antibodies against cell surface and basement membrane proteins a polyclonal antibody keratin. We have identified three basic types: basal, myoepithelial, epithelial cells. cells can be subdivided into immunologically related luminal type I, II, alveolar These five types appear at different stages either acquired or lost one antibody-defined antigens. cytoplasmic distribution several these antigens...

Mucin 1 (MUC1) is a transmembrane mucin expressed at the apical surface of epithelial cells mucosal surfaces. MUC1 has barrier function against bacterial invasion and well known for its aberrant expression glycosylation in adenocarcinomas. The extracellular domain contains variable number tandem repeats (VNTR) 20 amino acids, which are heavily O -linked glycosylated. Monoclonal antibodies VNTR powerful research tools with applications diagnosis treatment MUC1-expressing cancers. Here, we...

Episialin, the sialomucin encoded by MUCl gene is abundantly present at surface of various epithelial cells.It a transmembrane molecule that matures through several intermediate forms generated proteolysis and sequential addition processing numerous 0-linked glycans.Here we demonstrate one biosynthetic intermediates, premature form, which incompletely glycosylated appears cell surface.By neuraminidase protection assays show surface-associated episialin are constitutively internalized (0.9%...

MAM-6 is a major epithelial sialomucin which abundantly present at the apical surface of ductal and alveolar cells normal tissues on many different carcinoma cells.MAM-6, as defined by monoclonal antibodies, consists one or two sialylated glycoproteins with apparent molecular masses over 400 kDa under reducing well nonreducing conditions.The mobility number immunoprecipitated vary depending cell line origin.We have employed immunoprecipitation techniques to study biosynthesis glycosylation...

The mucin-like glycoprotein episialin (MUC1) is highly overproduced by a number of human carcinomas. We have shown previously in variety mammalian cell lines that overexpression this very large transmembrane molecule diminishes cellular adhesion, suggesting episialin/MUC1 may play an important role tumor invasion and metastasis. By using situ hybridization, we show here mRNA expression can be increased more than 10-fold breast carcinoma cells relative to the adjacent normal epithelium. In...

The ability of retroviruses and transposons to insert their genetic material into host DNA makes them widely used tools in molecular biology, cancer research gene therapy. However, these systems have biases that may strongly affect outcomes. To address this issue, we generated very large datasets consisting unselected integrations the mouse genome for Sleeping Beauty (SB) piggyBac (PB) transposons, Mouse Mammary Tumor Virus (MMTV). We analyzed (epi)genomic features generate bias maps at both...

Epidermal growth factor receptor (EGFR) is an important regulator of epithelial cell and survival in normal cancerous tissues a principal therapeutic target for cancer treatment. EGFR associated cells with the heavily glycosylated transmembrane mucin protein MUC1, natural ligand galectin-3 that overexpressed cancer. This study reveals expression surface MUC1 critical enhancer EGF-induced activation human breast colon cells. Both extracellular intracellular domains are involved but...

The gross majority of colorectal cancer cases results from aberrant Wnt/β-catenin signalling through adenomatous polyposis coli (APC) or CTNNB1 mutations. However, a subset human colon tumours harbour, mutually exclusive with APC and mutations, gene fusions in RSPO2 RSPO3, leading to enhanced expression these R-spondin genes. This suggested that RSPO activation can substitute for the most common mutations as an alternative driver intestinal cancer. Involvement RSPO3 tumour growth was...

Abstract In search of oncogenic drivers and mechanisms affecting therapy resistance in breast cancer, we identified Irs4 , a poorly studied member the insulin receptor substrate (IRS) family, as mammary oncogene by insertional mutagenesis. Whereas normally silent postnatal gland, IRS4 is found to be highly expressed subset cancers. We show that expression epithelial cells induces constitutive PI3K/AKT pathway hyperactivation, insulin/IGF1-independent cell proliferation, anchorage-independent...