Mucin

The availability of host and dietary carbohydrates in the gastrointestinal (GI) tract plays a key role in shaping the structure-function of the microbiota. In particular, some gut bacteria have the ability to forage on glycans provided by the mucus layer covering the GI tract. The O-glycan structures present in mucin are diverse and complex, consisting predominantly of core 1-4 mucin-type O-glycans containing α- and β- linked N-acetyl-galactosamine, galactose and N-acetyl-glucosamine. These core structures are further elongated and frequently modified by fucose and sialic acid sugar residues via α1,2/3/4 and α2,3/6 linkages, respectively. The ability to metabolize these mucin O-linked oligosaccharides is likely to be a key factor in determining which bacterial species colonize the mucosal surface. Due to their proximity to the immune system, mucin-degrading bacteria are in a prime location to influence the host response. However, despite the growing number of bacterial genome sequences available from mucin degraders, our knowledge on the structural requirements for mucin degradation by gut bacteria remains fragmented. This is largely due to the limited number of functionally characterized enzymes and the lack of studies correlating the specificity of these enzymes with the ability of the strain to degrade and utilize mucin and mucin glycans. This review focuses on recent findings unraveling the molecular strategies used by mucin-degrading bacteria to utilize host glycans, adapt to the mucosal environment, and influence human health.

The tight junction protein Claudin-1, a claudin family member, has been implicated in several gastro-intestinal pathologies including inflammatory bowel disease (IBD) and colorectal cancer (CRC). In this regard, we have demonstrated that claudin-1 expression in colon cancer cells potentiates their tumorigenic ability while in vivo expression of claudin-1 in the intestinal epithelial cells (IECs) promotes Notch-activation, inhibits goblet cell differentiation and renders susceptibility to mucosal inflammation. Notably, a key role of inflammation in colon cancer progression is being appreciated. Therefore, we examined whether inflammation plays an important role in claudin-1-dependent upregulation of colon carcinogenesis. APCmin mice were crossed with Villin-claudin-1 transgenic mice to generate APC-Cldn1 mice. H&E stained colon tissues were assessed for tumor number, size and histological grade. Additionally, microarray and qPCR analyses of colonic tumors were performed to assess mol...

The protein c-erbB-2, also known as Her2/neu, is a prognostic breast cancer marker assayed in tissue biopsies from women diagnosed with malignant tumors. Present studies suggest that soluble fragments of the c-erbB-2 oncogene may be released from the cell surface and become detectable in patients with carcinoma of the breast. Consequently, the purpose of this study was to assay the c-erbB-2 protein in the saliva and serum of women with and without carcinoma of the breast and to determine whether the protein possesses any diagnostic value. To determine the diagnostic utility of this oncogene, the soluble form of the c-erbB-2 protein was assayed in the saliva and serum using ELISA in three different groups of women. The three groups consisted of 57 healthy women, 41 women with benign breast lesions, and 30 women diagnosed with breast cancer. To compare the relative diagnostic utility of the c-erbB-2 protein, CA 15-3 was also measured. The CA 15-3 measurements served as a "gold st...

Breast cancer is a major health problem in underdeveloped countries including Sudan. Immunohistochemical typing is important for diagnosing and understanding the biology of such heterogeneous disease. To the best of our knowledge, no study has investigated the association between estrogen receptors (ER) expression and carbohydrates in breast tissue. Mammographic high density, a major risk factor, is partially attributed to carbohydrates. This study aimed to determine the type of carbohydrates in malignant and benign breast lesions and detect if there is any association between ER expression and carbohydrates using histochemical and immunohistochemical methods. A total of 60 diagnosed samples of different breast lesions were reexamined for ER status by immunohistochemistry (IHC) and for carbohydrates by histochemical staining methods i.e. periodic acid Schiff (PAS) and alcian blue. Strong relationship was discovered between ER positivity and presence of acid mucin, but not with sulfated mucin. Furthermore, strong relationship was found between ER positivity and PAS positive materials, but not with glycogen. Since there was a significant correlation between ER and carbohydrates, these positive PAS materials might be PAS positive acid mucin. These findings are useful in understanding the behavior of breast lesions. Also, these findings suggested an underlying molecular relationships and that ER expression might be predicted using histochemical demonstration of carbohydrates in female breast tissue particularly when immunohistochemistry is out of reach.

Intestinal metaplasia (IM) is part of a stepwise sequence of alterations of the gastric mucosa, leading ultimately to gastric cancer, and is strongly associated with chronic Helicobacter pylori infection. The molecular mechanisms underlying the onset of IM remain elusive. The aim of this study was to assess the putative involvement of two intestine-specific transcription factors, CDX1 and CDX2, in the pathogenesis of gastric IM and gastric carcinoma. Eighteen foci of IM and 46 cases of gastric carcinoma were evaluated by immunohistochemistry for CDX1 and CDX2 expression. CDX1 was expressed in all foci of IM and in 41% of gastric carcinomas; CDX2 was expressed in 17/18 foci of IM and in 54% of gastric carcinomas. In gastric carcinomas, a strong association was observed between the expression of CDX1 and CDX2, as well as between the intestinal mucin MUC2 and CDX1 and CDX2. No association was observed between the expression of CDX1 and CDX2 and the histological type of gastric carcinoma. In conclusion, these results show that aberrant expression of CDX1 and CDX2 is consistently observed in IM and in a subset of gastric carcinomas. The association of CDX1 and CDX2 with expression of the intestinal mucin MUC2, both in IM and in gastric carcinoma, indirectly implies that CDX1 and CDX2 may be involved in intestinal differentiation along the gastric carcinogenesis pathway. Copyright © 2002 John Wiley & Sons, Ltd.

The implantation process involves complex and synchronized molecular and cellular events between the uterus and the implanting embryo. These events are regulated by paracrine and autocrine factors. Trophoblast invasion and migration through the uterine wall is mediated by molecular and cellular interactions, controlled by the trophoblast and the maternal microenvironment. This review is focused on the molecular constituents of the human trophoblast, their actions and interactions, including interrelations with the uterine endometrium.

In health, the airways are lined by a layer of protective mucus gel that sits atop a watery periciliary fluid. Mucus is an adhesive, viscoelastic gel, the biophysical properties of which are largely determined by entanglements of long polymeric gel-forming mucins, MUC5AC and MUC5B. This layer entraps and clears bacteria and inhibits bacterial growth and biofilm formation. It also protects the airway from inhaled irritants and from fluid loss. In diseases such as cystic fibrosis there is almost no mucin (and thus no mucus) in the airway; secretions consist of inflammatory-cell derived DNA and filamentous actin polymers, which is similar to pus. Retention of this airway pus leads to ongoing inflammation and airway damage. Mucoactive medications include expectorants, mucolytics, and mucokinetic drugs. Expectorants are meant to increase the volume of airway water or secretion in order to increase the effectiveness of cough. Although expectorants, such as guaifenesin (eg, Robatussin or M...

Increased expression of the epithelial mucin MUC1 has been linked to tumor aggressiveness in human breast carcinoma. Recent studies have demonstrated that overexpression of MUC1 interferes with cell-substrate and cell-cell adhesion by masking cell surface integrins and E-cadherin. Additionally, the cytoplasmic tail of MUC1 is involved in signal transduction and interactions with catenins. In the present study, we have examined the in vitro expression of MUC1 mRNA and protein in a panel of 14 human breast cancer cell lines using northern blotting, western blotting, immunocytochemistry, and flow cytometry. Considerable variability of expression was noted not only between cell lines but also within several individual lines. Many cell lines such as BT 20, KPL-1, and T47D expressed abundant MUC1 whilst others such as MDA-MB-231 and MCF-7 showed intermediate expression, and MDA-MB-435 and MDA-MB-453 expressed very low levels. Low levels of MUC1 expression were associated with decreased expression of cytokeratin and increased expression of vimentin. Additionally, 12 of the cell lines were established as xenografts in immunocompromised (SCID) mice, and MUC1 expression in both the primary tumors as well as metastases was assessed immunohistochemically. In general, in vivo expression mirrored in vitro expression, although there was reduced in vivo expression in T47D and ZR-75-1 xenografts. Although we showed no correlation between tumorigenicity or metastasis and MUC1 expression, this study will assist development of experimental models to assess the influence of MUC1 of on breast cancer progression.

MUC1 is a large transmembrane glycoprotein and oncogene expressed by epithelial cells and overexpressed and underglycosylated in cancer cells. The MUC1 cytoplasmic subunit (MUC1-C) can translocate to the nucleus and regulate gene expression. It is frequently assumed that the MUC1 extracellular subunit (MUC1-N) does not enter the nucleus. Based on an unexpected observation that MUC1 extracellular domain antibody produced an apparently nucleus-associated staining pattern in trophoblasts, we have tested the hypothesis that MUC1-N is expressed inside the nucleus. Three different antibodies were used to identify MUC1-N in normal epithelial cells and tissues as well as in several cancer cell lines. The results of immunofluorescence and confocal microscopy analyses as well as subcellular fractionation, Western blotting, and siRNA/shRNA studies, confirm that MUC1-N is found within nuclei of all cell types examined. More detailed examination of its intranuclear distribution using a proximity...

The aim of this work was to investigate if serum and salivary auto-antibodies, isotypes IgG and IgM, against HER2 and MUC1 tandem repeat fragments could play a role in breast cancer screening. Our case-control study was conducted in breast cancer patients, in early stages (n=29), at the gynecology service, Maternity Souissi Hospital, Rabat, Morocco and healthy woman (n=31). Salivary and serum auto-antibodies against HER2 and MUC1 (tandem repeat) were assessed by enzyme-linked immunosorbent assay (ELISA) and compared between patients and healthy women using the Mann-Whitney U test. A P-value <0.05 was considered to be statistically significant. Our data showed higher expression of all serum and salivary autoantibodies in patients as compared to healthy women p<0.05. However, serum IgM anti-MUC1 expression did not show a significant difference between cases and controls (p=0.79). Similarly, salivary IgG anti-HER2 expression did not differ (p=0.15). The correlation between the di...

Sclerosing epitheloid fibrosarcoma is a rare, histologically well-defined member of adult fibrosarcoma group of soft tissue tumors. Its main histological features are nests and cords of rounded tumor cells surrounded by hyalinized collagenous stroma. Epitheloid appearance with marked sclerosis and infiltrating growth pattern, along with occasional immunohistochemical positivity for epithelial markers may be highly suggestive of infiltrating carcinoma. Despite of bland cytological features clinical course is often protracted with a high local recurrence rate and late metastases. In this report, we present histopathological characteristics of two cases of sclerosing epitheloid fibrosarcoma, together with their clinical presentation, follow-up information and differential diagnosis.