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Journal of Clinical Pathology Oct 1996
Topics: Adenocarcinoma; Coloring Agents; History, 17th Century; History, 18th Century; History, 19th Century; History, 20th Century; History, Ancient; Humans; Mucins; Staining and Labeling
PubMed: 8943740
DOI: 10.1136/jcp.49.10.787 -
British Medical Journal Sep 1951
Topics: Humans; Mucins
PubMed: 14869681
DOI: No ID Found -
Pharmacology & Therapeutics Mar 2009Mucus production is a primary defense mechanism for maintaining lung health. However, the overproduction of mucin (the chief glycoprotein component of mucus) is a common... (Review)
Review
Mucus production is a primary defense mechanism for maintaining lung health. However, the overproduction of mucin (the chief glycoprotein component of mucus) is a common pathological feature in asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), and lung cancer. Although it is associated with disease progression, effective therapies that directly target mucin overproduction and hypersecretion are lacking. Recent advances in our understanding of the control of mucin gene expression in the lungs, the cells that produce airway mucins, and the mechanisms used for releasing them into the airways have provided new potentials for the development of efficacious interventions that will be discussed in this review.
Topics: Cystic Fibrosis; Exocytosis; Gene Expression Regulation; Humans; Lung; Mucins; Mucus; Pulmonary Disease, Chronic Obstructive; Respiratory System; Respiratory System Agents; Signal Transduction
PubMed: 19059283
DOI: 10.1016/j.pharmthera.2008.11.001 -
Nature Chemical Biology Jul 2022Mucins are large gel-forming polymers inside the mucus barrier that inhibit the yeast-to-hyphal transition of Candida albicans, a key virulence trait of this important...
Mucins are large gel-forming polymers inside the mucus barrier that inhibit the yeast-to-hyphal transition of Candida albicans, a key virulence trait of this important human fungal pathogen. However, the molecular motifs in mucins that inhibit filamentation remain unclear despite their potential for therapeutic interventions. Here, we determined that mucins display an abundance of virulence-attenuating molecules in the form of mucin O-glycans. We isolated and cataloged >100 mucin O-glycans from three major mucosal surfaces and established that they suppress filamentation and related phenotypes relevant to infection, including surface adhesion, biofilm formation and cross-kingdom competition between C. albicans and the bacterium Pseudomonas aeruginosa. Using synthetic O-glycans, we identified three structures (core 1, core 1 + fucose and core 2 + galactose) that are sufficient to inhibit filamentation with potency comparable to the complex O-glycan pool. Overall, this work identifies mucin O-glycans as host molecules with untapped therapeutic potential to manage fungal pathogens.
Topics: Candida albicans; Fucose; Mucins; Polysaccharides; Virulence
PubMed: 35668191
DOI: 10.1038/s41589-022-01035-1 -
Bulletin Du Cancer Mar 2007MUC1 is a large, highly glycosylated protein expressed on the apical membrane of many epithelial cells. With other members of the mucin family it contributes to the... (Review)
Review
MUC1 is a large, highly glycosylated protein expressed on the apical membrane of many epithelial cells. With other members of the mucin family it contributes to the protection and function of mucosal cells. The intracellular part of the protein may also participate in signal transduction pathway, through multiple interactions with intracellular proteins. Overexpression of MUC1 is frequently observed in the majority of epithelial cancers and even in some haematological malignancies. In tumor cells, MUC1 loses apical distribution and is hypoglycosylated. These cancer-associated changes render it antigenic and make it an attractive target for a specific cancer immunotherapy. Several MUC1-based therapeutic cancer vaccines are currently under clinical investigation.
Topics: Antigens, Neoplasm; Cancer Vaccines; Humans; Membrane Glycoproteins; Mucin-1; Mucins; Neoplasm Proteins; Neoplasms
PubMed: 17371767
DOI: No ID Found -
Annals of Surgical Oncology May 2008Pseudomyxoma peritonei (PMP) is characterized by peritoneal tumors arising from a perforated appendiceal adenoma or adenocarcinoma, but associated entry of enteric... (Comparative Study)
Comparative Study
Pseudomyxoma peritonei: is disease progression related to microbial agents? A study of bacteria, MUC2 AND MUC5AC expression in disseminated peritoneal adenomucinosis and peritoneal mucinous carcinomatosis.
BACKGROUND AND AIMS
Pseudomyxoma peritonei (PMP) is characterized by peritoneal tumors arising from a perforated appendiceal adenoma or adenocarcinoma, but associated entry of enteric bacteria in the peritoneum has not been considered as a cofactor. Because Gram-negative organisms can upregulate MUC2 mucin gene expression, we determined whether bacteria were detectable in PMP tissues.
METHODS
In situ hybridization was performed on resection specimens from five control subjects with noninflamed, nonperforated, non-neoplastic appendix and 16 patients with PMP [six with disseminated peritoneal adenomucinosis (DPAM) and 10 with peritoneal mucinous carcinomatosis (PMCA)]. Specific probes were designed to recognize: (1) 16S rRNA common to multiple bacteria or specific to H. pylori; (2) H. pylori cagA virulence gene; or (3) MUC2 or MUC5AC apomucins. Specimens from one patient with PMCA were examined by ultrastructural immunohistochemistry. Bacterial density and apomucin expression were determined in four histopathological compartments (epithelia, inflammatory cells, stroma, and free mucus).
RESULTS
Enteric bacteria were detected in all specimens. Bacterial density and MUC2 expression were significantly (p < 0.05) higher in PMCA than in DPAM and controls and were highest in free mucin. MUC2 was also expressed in dysplastic epithelia and in associated inflammatory cells. MUC2 expression was significantly correlated with bacterial density.
CONCLUSIONS
Multiple enteric bacteria are present in PMP, and bacterial density and MUC2 expression is highest in the malignant form of PMP. Based on these observations, we propose that the bacteria observed in PMP may play a role in the mucinous ascites and perhaps promote carcinogenesis.
Topics: Adenocarcinoma, Mucinous; Appendix; Biomarkers, Tumor; Case-Control Studies; DNA Probes; Disease Progression; Gene Expression Regulation, Neoplastic; Helicobacter Infections; Helicobacter pylori; Humans; In Situ Hybridization; Microscopy, Electron, Transmission; Mucin 5AC; Mucin-2; Mucins; Peritoneal Neoplasms; Prognosis; Pseudomyxoma Peritonei; RNA Probes
PubMed: 18299935
DOI: 10.1245/s10434-007-9778-9 -
Seminars in Cell & Developmental Biology Aug 2010Newly emerging genetic studies have revealed that a subset of the family of glycosyltransferases responsible for the formation of mucin-type O glycans is essential for... (Review)
Review
Newly emerging genetic studies have revealed that a subset of the family of glycosyltransferases responsible for the formation of mucin-type O glycans is essential for normal development. As additional genetic, biochemical and physical tools are developed to interrogate the complex structure and surface location of this under-studied class of carbohydrate, no doubt additional roles will be elucidated.
Topics: Eukaryota; Glycosylation; Glycosyltransferases; Mucins; Polysaccharides
PubMed: 20144722
DOI: 10.1016/j.semcdb.2010.02.001 -
Biological Chemistry Jan 1998Mucins are widely distributed in mucous secretion fluids or are associated with plasma membranes. Up to now 9 genes of epithelial mucins have been identified,... (Review)
Review
Mucins are widely distributed in mucous secretion fluids or are associated with plasma membranes. Up to now 9 genes of epithelial mucins have been identified, distributed over five chromosomes. Superposed on the genetic diversity, each type of mucin displays heterogeneity in oligosaccharide composition, including the terminal sugar residues. On top of that there is variation between individuals brought about by blood group antigens. Heterogeneity is further incited by the degree of sulfation. This tremendous structural heterogeneity endows mucin molecules with properties suggestive for a multifunctional role. The major biological function assigned to mucins is still the protection of tissues covered by the mucous gel. Current knowledge on the specific biological functions of the sulfate residues is fragmentary and periphrastic. Glycosylation including sulfation appears to be subject to modification under pathological conditions. There is evidence that sulfation rate-limits bacterial degradation of mucins. Moreover, accumulating data focus towards their involvement in recognition phenomena. Sulfate residues on blood group related structures provoke specific epitopes for selective interaction with microorganisms e.g. Helicobacter pylori. A distinct class of mucins acts as ligands for selectins, crucial in cellular recognition processes like cellular homing of lymphocytes. Whereas in earlier days mucins were only seen as water-binding molecules, protecting the underlying mucosa against harmful agents, the current picture of these molecules is characterized by the selective interaction with their environment, including epithelial-, and endothelial cells and microorganisms, thereby regulating a great number of biological processes. However, the specific role of sulfate remains to be further elucidated.
Topics: Gene Expression; Glycoproteins; Glycosylation; Humans; Mucins; Oligosaccharides; Salivary Glands; Selectins; Sulfates
PubMed: 9504711
DOI: 10.1515/bchm.1998.379.1.1 -
The American Journal of Pathology Mar 2023Cancer antigen 125 (CA125) is one of the mucin family proteins and is a serum tumor marker for various tumors, such as ovarian cancer, endometrial cancer, pancreatic...
Cancer antigen 125 (CA125) is one of the mucin family proteins and is a serum tumor marker for various tumors, such as ovarian cancer, endometrial cancer, pancreatic cancer, and bladder cancer. CA125 is used to distinguish between benign and malignant tumors, monitor the response to chemotherapy, and detect relapse after initial treatment. Recently, CA125 was reported to be involved in chemoresistance through the physical characteristics of mucin or by modifying the immune tumor-microenvironment. However, the relationship between CA125 expression and chemoresistance in bladder cancer is still unclear. In this study, the clinicopathologic features of bladder cancer with CA125 expression and the status of the tumor-microenvironment related to gemcitabine/cisplatin resistance were investigated using publicly available data sets (Cancer Genome Atlas Expression, GSE169455 data set) from the cBioPortal website, the National Center for Biotechnology Information website, and an in-house case collection of bladder cancer. The cases with CA125 expression had poorer disease-free and overall survival rates than those without CA125 expression. A mucinous area surrounding cancer cells was frequently detected in cases with CA125 expression (81%; 13/16 cases). CA125 expression was also related to the immunosuppressive tumor-microenvironment through the infiltration of immunosuppressive immune cells, such as regulatory T cells and M2 macrophages. These results suggest that the status of tumor-microenvironment associated with CA125 is involved in gemcitabine/cisplatin resistance in bladder cancer.
Topics: Humans; Biomarkers, Tumor; CA-125 Antigen; Cisplatin; Gemcitabine; Mucins; Neoplasm Recurrence, Local; Tumor Microenvironment; Urinary Bladder Neoplasms; Drug Resistance, Neoplasm
PubMed: 36586479
DOI: 10.1016/j.ajpath.2022.12.005 -
World Journal of Gastroenterology Jul 2013To investigate mucin expression profiles in colorectal carcinoma (CRC) histological subtypes with regard to clinicopathologic variables and prognosis. (Comparative Study)
Comparative Study
AIM
To investigate mucin expression profiles in colorectal carcinoma (CRC) histological subtypes with regard to clinicopathologic variables and prognosis.
METHODS
Mucin (MUC)2 and MUC5AC expressions were assessed by immunohistochemistry for a total of 250 CRC cases that underwent surgical resection. CRCs included 63 well-to-moderately differentiated adenocarcinomas (WMDAs), 91 poorly differentiated adenocarcinomas (PDAs), 81 mucinous adenocarcinoma (MUAs), and 15 signet-ring cell carcinomas (SRCCs). MUC2 and MUC5AC were scored as positive when ≥ 25% and ≥ 1% of cancer cells were stained positive, respectively. The human mutL homolog 1 and human mutS homolog 2 expressions were assessed by immunohistochemistry in PDAs to investigate mismatch-repair (MMR) status. Tumors that did not express either of these two were considered MMR-deficient. Results were analyzed for associations with clinicopathologic variables and the prognosis in individual histological CRC subtypes.
RESULTS
MUC2-positive and MUC5AC-positive WMDA percentages were 49.2% and 30.2%, respectively. In contrast, MUC2-positive and MUC5AC-positive PDA percentages were 9.5% and 51.6%, respectively. MUC2 levels tended to decrease and MUC5AC levels tended to increase from WMDA to PDA. In 21 tumors comprising both adenoma and adenocarcinoma components in a single tumor (4 WMDAs, 7 PDAs, and 10 MUAs), MUC2 was significantly downregulated in PDA and MUC5AC was downregulated in PDA and MUA in the adenoma-carcinoma sequence. These results suggested that MUC2 levels might be associated with malignant potential and that MUC5AC expression was an early event in tumorigenesis. Despite worse prognoses than WMDA, high MUC2 expression levels were maintained in MUA (95.1%) and SRCC (71.5%), which suggested a pathogenesis for these subtypes distinct from that of WMDA. No significant associations were found between MUC2 expression and any clinicopathologic variables in any histological subtype. MUC5AC expression in PDA was closely associated with right-sided location (P = 0.017), absence of nodal metastasis (P = 0.010), low tumor node metastasis stage (P = 0.010), and MMR deficiency (P = 0.003). MUC2 expression in WMDA was a marginal prognostic factor for recurrence/metastasis-free survival (RFS) by univariate Cox analysis (P = 0.077) but not by multivariate Cox analysis (P = 0.161). MUC5AC expression in PDA was a significant prognostic factor for RFS by univariate Cox analysis (P = 0.007) but not by multivariate Cox analysis (P = 0.104). Kaplan-Meier curves and log-rank tests revealed that MUC2 expression was marginally associated with a better WMDA prognosis [P = 0.064 for RFS and P = 0.172 for overall survival (OS)] but not for PDA. In contrast, MUC5AC expression was significantly and marginally associated with a better PDA prognosis in terms of RFS and OS, respectively (P = 0.004 for RFS and P = 0.100 for OS), but not for WMDA and MUA.
CONCLUSION
Mucin core protein expression profiles and clinical significance differ according to histological CRC subtypes. This may reflect different pathogeneses for these tumors.
Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adult; Aged; Aged, 80 and over; Carcinoma, Signet Ring Cell; Colorectal Neoplasms; Diagnosis, Differential; Female; Humans; Male; Middle Aged; Mucin 5AC; Mucin-2; Mucins; Phenotype; Prognosis; Retrospective Studies
PubMed: 23840140
DOI: 10.3748/wjg.v19.i25.3957