Gastric M1 mucin, an early oncofetal marker of colon carcinogenesis, is encoded by the MUC5AC gene

Bara, Jacques; Chastre, Eric; Mahiou, Jérôme; Singh, Rupachandra L.; Forgue‐Lafitte, Marie‐Elisabeth; Hollande, E; Godeau, François

doi:10.1002/(sici)1097-0215(19980302)75:5<767::aid-ijc17>3.0.co;2-3

Cited by 110 publications

(64 citation statements)

References 15 publications

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“…45M1 and CLH5 were examined as the gastric-phenotype markers, and Ccp58 and 56C6 were examined as the intestinal-phenotype markers. HGM is synonymous with MUC5AC and the antibody is known to react with surface foveolar cells in the stomach (Bara et al, 1998;Nollet et al, 2002). MUC6 glycoprotein is expressed in the mucous cells of the neck zone of the oxyntic mucosa and in the antral glands (De Bolos et al, 1995;Reis et al, 1999).…”

Section: Analysis Of Expressions Of Phenotypic Markersmentioning

confidence: 99%

Differences in the histological findings, phenotypic marker expressions and genetic alterations between adenocarcinoma of the gastric cardia and distal stomach

et al. 2007

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Adenocarcinoma of the gastric cardia (C-Ca) is possibly a specific subtype of gastric carcinoma. The purpose of this study was to clarify the differences in the clinicopathological characteristics between C-Ca and adenocarcinoma of the distal stomach (D-Ca), and also the differences in the expressions of gastric and intestinal phenotypic markers and genetic alterations between the two. The clinicopathological findings in 72 cases with C-Ca were examined and compared with those in 170 cases with D-Ca. The phenotypic marker expressions examined were those of human gastric mucin (HGM), MUC6, MUC2 and CD10. Furthermore, the presence of mutations in the APC, K-ras and p53 genes and the microsatellite instability status of the tumour were also determined. C-Ca was associated with a significantly higher incidence of differentiated-type tumours and lymphatic vessel invasion (LVI) as compared with D-Ca (72.2 vs 48.2%, P ¼ 0.0006 and 72.2 vs 55.3%, P ¼ 0.0232, respectively). Oesophageal invasion by the tumour beyond the oesophago-gastric junction (OGJ) was found in 56.9% of cases with C-Ca; LVI in the area of oesophageal invasion was demonstrated in 61% of these cases. Also, LVI was found more frequently in cases of C-Ca with oesophageal invasion than in those without oesophageal invasion (82.9 vs 58.1%, P ¼ 0.0197). The incidence of undifferentiated-type tumours was significantly higher in cases with advanced-stage C-Ca than in those with early-stage C-Ca (5 vs 36.5%, P ¼ 0.0076). A significantly greater frequency of HGM expression in early-stage C-Ca and significantly lower frequency of MUC2 expression in advanced-stage C-Ca was observed as compared with the corresponding values in cases of D-Ca (78.9 vs 52.2%, P ¼ 0.0402 and 51.5 vs 84.6%, P ¼ 0.0247, respectively). Mutation of the APC gene was found in only one of all cases of C-Ca, and the frequency of mutation of the APC gene was significantly lower in cases of C-Ca than in those of D-Ca (2.4 vs 20.0%, P ¼ 0.0108). The observations in this study suggest that C-Ca is a more aggressive tumour than D-Ca. The differences in biological behavior between C-Ca and D-Ca may result from the different histological findings in the wall of the OGJ and the different genetic pathways involved in the carcinogenesis.

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Section: Analysis Of Expressions Of Phenotypic Markersmentioning

confidence: 99%

Differences in the histological findings, phenotypic marker expressions and genetic alterations between adenocarcinoma of the gastric cardia and distal stomach

et al. 2007

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“…45M1 recognises the mucin epitope located in the peptide core of HGM, which is synonymous with MUC5AC. This antibody is known to react with surface foveolar cells in the stomach (Bara et al, 1998;Nollet et al, 2002). MUC6 glycoprotein is expressed in mucous cells of the neck zone of oxyntic mucosa and in antral glands (De Bolos et al, 1995;Reis et al, 1999;Machado et al, 2000).…”

Section: Immunohistochemical Stainingmentioning

confidence: 99%

Gastric and intestinal phenotypic marker expression in gastric carcinomas and recurrence pattern after surgery-immunohistochemical analysis of 213 lesions-

et al. 2004

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Both gastric and intestinal phenotypic markers are known to be expressed in gastric carcinomas, irrespective of their histologic type. In the present study, the relation between gastric and intestinal phenotypic marker expression in gastric carcinomas and the recurrence pattern after surgery was examined. The phenotypic marker expression of the tumour was determined by examining the expression of human gastric mucin (HGM), MUC6, MUC2 and CD10 in 213 advanced gastric carcinomas in 213 patients who had undergone a curative resection (97 died from recurrent gastric carcinoma and 116 were alive without recurrence at the end of the follow-up period). Tumours were classified into gastric (G), gastric and intestinal mixed (GI), intestinal (I) or unclassified (UC) phenotypes according to the immunopositivity of HGM, MUC6, MUC2 and CD10 stainings. The incidence of HGM-positive tumours and MUC2-negative tumours was significantly higher in tumours with peritoneal recurrence than in tumours without recurrence (73.3%, 44 out of 60 cases vs 54.3%, 63 out of 116 (P ¼ 0.022); and 70.0%, 42 out of 60 vs 38.8%, 45 out of 116 (P ¼ 0.0002), respectively). The incidence of G-phenotype tumours was also significantly higher in tumours with peritoneal recurrence than in tumours without recurrence (58.3%, 35 out of 60 cases vs 28.4%, 33 out of 116 (P ¼ 0.0002)). The incidence of MUC2-negative tumours and CD10-positive tumours was significantly higher in tumours with haematogenous recurrence than in tumours without recurrence (62.5%, 20 out of 32 cases vs 38.8%, 45 out of 116 (P ¼ 0.028); and 43.8%, 14 out of 32 vs 23.3%, 27 out of 116 (P ¼ 0.039); respectively). Our present findings show that the gastric and intestinal phenotypic marker expression of the tumour, determined by immunohistochemical staining for HGM, MUC6, MUC2 and CD10, can be used to predict the pattern of gastric carcinoma recurrence after curative resection.

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“…18 -20 On the other hand, de novo appearance of a secreted mucin normally found in the stomach, MUC5AC, has been described in colon carcinomas. [21][22][23] Thus, mucinous differentiated cells are present in colorectal carcinomas and more particularly in mucinous carcinomas and in signet ring cell carcinomas. Until now, the significance of a differentiation characteristic into a mucin-secreting phenotype with regard to the tumor development is still unknown.…”

Section: Abstract: Colon Carcinoma Cells; E-cadherin; Mucins; Heparamentioning

confidence: 99%

“…The mouse monoclonal antibody MB2 was raised against MCF7/AZ cells and selected for functional inactivation of E-cadherin. 26 Mouse monoclonal anti-MUC1 (214D4 27 ) and anti-MUC5AC (21M1 22 ) antibodies, and rabbit polyclonal anti-E-cadherin antibody (␣-UMT) were a gift, respectively, from Dr. J. Hilkens (The Netherlands Cancer Institute, Amsterdam), Dr. J. Bara (INSERM U-482, Saint-Antoine Hospital, Paris, France) and Dr. J. Behrens (Friedrich-Miescher Laboratory der Max Planck society in Tübingen). The polyclonal anti-MUC5AC antibody (LUM5-1 28 ) was a gift from Dr. Carlstedt (Lund University, Sweden).…”

Section: Antibodiesmentioning

confidence: 99%

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Requirement of both mucins and proteoglycans in cell‐cell dissociation and invasiveness of colon carcinoma HT‐29 cells

Truant

Bruyneel

Gouyer

et al. 2003

Intl Journal of Cancer

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Key words: colon carcinoma cells; E-cadherin; mucins; heparan sulfate proteoglycansEpithelial E-cadherin, a component of the adherens junctions, is crucial for the organization and maintenance of differentiated epithelia. 1 The extracellular NH2-terminal domain of this transmembrane glycoprotein mediates cell-cell adhesion in a homophilic and Ca 2ϩ -dependent way. The COOH-terminal domain binds to the actin cytoskeleton via ␣-catenin and ␤-catenin or plakoglobin. 2 Studies in cancer cell lines have shown that changes in the structure or in the expression of the components of the E-cadherin/␤-catenin complex result in the suppression of cell-cell adhesion and in the expression of an invasive phenotype. [3][4][5][6][7][8] In cancer, the maintenance of the epithelia is lost and dissociation of cells is associated with metastatic dissemination. This phenomenon can occur through a decrease in the expression level of E-cadherin and, regarding colon cancer, such decrease has been related to the tumor grade and clinical outcome. 9 At the genomic level, loss of E-cadherin expression does not occur as a result of mutation of E-cadherin gene, whereas mutations of ␤-catenin were found in a small proportion of colon cancers. 10 -12 In another way, E-cadherin-mediated cell-cell adhesion may be modulated by the mucin-like glycoprotein MUC1, which is often overexpressed in cancer. MUC1, also termed episialin, is a membrane-associated glycoprotein composed of a membrane anchor and a mucin-like ectodomain. 13 In human ZR-75-1 breast cancer cells, the cytoplasmic domain of MUC1 was shown to bind ␤-catenin, leading to a decrease of E-cadherin-catenin complex and an anti-adhesion effect. 14 On the other hand, MUC1 was shown to cause steric hindrance of adhesion molecules like E-cadherin, through its large negatively charged extracellular domain, which contains many oligosaccharide side chains. 15,16 Proteoglycans were also shown to disturb the function of E-cadherin through steric hindrance in variants of the murine mammary gland cell line NMuMG and the canine epithelial kidney cell line MDCK. 17 During colorectal carcinogenesis, the expression of MUC1 was found upregulated, particularly in later stages of the disease. 18 -20 On the other hand, de novo appearance of a secreted mucin normally found in the stomach, MUC5AC, has been described in colon carcinomas. [21][22][23] Thus, mucinous differentiated cells are present in colorectal carcinomas and more particularly in mucinous carcinomas and in signet ring cell carcinomas. Until now, the significance of a differentiation characteristic into a mucin-secreting phenotype with regard to the tumor development is still unknown.To investigate the role of mucins in the invasive properties of colon carcinoma cells, the HT-29 cell line is an appropriate model, as the cells of this cell line express different phenotypes: besides a majority of undifferentiated cells (Ͼ95%), a small proportion of cells presents a capacity to differentiate into a mucinous phenotype or into an enterocyte-like ...

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Gastric M1 mucin, an early oncofetal marker of colon carcinogenesis, is encoded by the MUC5AC gene

Cited by 110 publications

References 15 publications

Differences in the histological findings, phenotypic marker expressions and genetic alterations between adenocarcinoma of the gastric cardia and distal stomach

Differences in the histological findings, phenotypic marker expressions and genetic alterations between adenocarcinoma of the gastric cardia and distal stomach

Gastric and intestinal phenotypic marker expression in gastric carcinomas and recurrence pattern after surgery-immunohistochemical analysis of 213 lesions-

Requirement of both mucins and proteoglycans in cell‐cell dissociation and invasiveness of colon carcinoma HT‐29 cells

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