Mucin antibodies - new tools in diagnosis and therapy of cancer

Wittel, Uwe A.; Goel, Apollina; Varshney, Grish C.; Batra, Surinder K.

doi:10.2741/wittel

Cited by 22 publications

(19 citation statements)

References 70 publications

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“…Underglycosylation of mucins in cancers is well known and could explain the detection of membrane staining in the other cases of adenocarcinomas. 36 MUC4 gene expression has been previously reported in 34 lung adenocarcinomas (17 of nonbronchioloalveolar and 17 of bronchioloalveolar type), by in situ hybridization 33 whatever the histological subtype according to the WHO classification. 34 MUC4 mRNA expression has also been described in lung carcinomas by Northern blot analysis and RT-PCR.…”

Section: Discussionmentioning

confidence: 94%

Diagnostic value of MUC4 immunostaining in distinguishing epithelial mesothelioma and lung adenocarcinoma

et al. 2004

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The distinction between pleural malignant mesothelioma and pleural infiltration by adenocarcinomas has complex therapeutic and medicolegal implications. Although the panel of adenocarcinoma-associated antibodies and one or two mesothelioma markers is useful in this purpose, most of these antibodies are not totally specific. We determined the diagnostic value of MUC4 immunostaining in this issue. MUC4 gene expression was also studied by in situ hybridization and RT-PCR. MUC4 is a membrane-bound mucin that has been suggested to be implicated in malignant progression in humans and rats. The MUC4 gene is expressed in various normal epithelial tissues of endodermic origin and carcinomas. In the respiratory tract, MUC4 transcripts have been detected in normal respiratory epithelium and lung carcinomas. MUC4 protein was expressed in 32 of 35 (91.4%) lung adenocarcinomas on paraffin-embedded tissue. None of the 41 malignant mesotheliomas nor the 32 cases of benign mesothelial cells expressed MUC4 at the protein and mRNA levels. We conclude that MUC4 is a very specific (100%) and sensitive (91.4%) marker of lung adenocarcinomas on paraffin-embedded tissue that could be useful in diagnostic practice in the distinction between malignant mesothelioma and adenocarcinoma.

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Section: Discussionmentioning

confidence: 94%

Diagnostic value of MUC4 immunostaining in distinguishing epithelial mesothelioma and lung adenocarcinoma

et al. 2004

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“…Information on MUC-specific polyclonal or monoclonal antibodies used to investigate human MUC or rodent Muc mucins in respiratory tract cells or secretions is provided in Table 4. Detailed information on monoclonal antibodies used to investigate mucin expression in epithelial tissues and in cancer studies is available (304).…”

Section: Molecular Tools For Muc Identificationmentioning

confidence: 99%

Respiratory Tract Mucin Genes and Mucin Glycoproteins in Health and Disease

Rose

Voynow²

2006

Physiological Reviews

956

892

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This review focuses on the role and regulation of mucin glycoproteins (mucins) in airway health and disease. Mucins are highly glycosylated macromolecules (≥50% carbohydrate, wt/wt). MUC protein backbones are characterized by numerous tandem repeats that contain proline and are high in serine and/or threonine residues, the sites of O-glycosylation. Secretory and membrane-tethered mucins contribute to mucociliary defense, an innate immune defense system that protects the airways against pathogens and environmental toxins. Inflammatory/immune response mediators and the overproduction of mucus characterize chronic airway diseases: asthma, chronic obstructive pulmonary diseases (COPD), or cystic fibrosis (CF). Specific inflammatory/immune response mediators can activate mucin gene regulation and airway remodeling, including goblet cell hyperplasia (GCH). These processes sustain airway mucin overproduction and contribute to airway obstruction by mucus and therefore to the high morbidity and mortality associated with these diseases. Importantly, mucin overproduction and GCH, although linked, are not synonymous and may follow from different signaling and gene regulatory pathways. In section i, structure, expression, and localization of the 18 human MUC genes and MUC gene products having tandem repeat domains and the specificity and application of MUC-specific antibodies that identify mucin gene products in airway tissues, cells, and secretions are overviewed. Mucin overproduction in chronic airway diseases and secretory cell metaplasia in animal model systems are reviewed in section ii and addressed in disease-specific subsections on asthma, COPD, and CF. Information on regulation of mucin genes by inflammatory/immune response mediators is summarized in section iii. In section iv, deficiencies in understanding the functional roles of mucins at the molecular level are identified as areas for further investigations that will impact on airway health and disease. The underlying premise is that understanding the pathways and processes that lead to mucus overproduction in specific airway diseases will allow circumvention or amelioration of these processes.

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“…They form lubricants protective selective barrier on epithelial surfaces, and modulate cell-cell and cell-extracellular matrix interactions, lymphocyte trafficking and anti-immune recognition. Their expression is regulated by several cytokines and local and endocrine hormones [3][4][5]. It was postulated that the increased occurrence of apoptosis in the gastric epithelium might be of pathophysiological importance in the development of stress lesions.…”

Section: Introductionmentioning

confidence: 99%