Mucin production by human colonic carcinoma cells correlates with their metastatic potential in animal models of colon cancer metastasis.

Bresalier, Robert S.; Niv, Yaron; Byrd, James C.; Duh, Quan‐Yang; Toribara, Neil W.; Rockwell, Richard; Dahiya, Rajvir; Kim, Y. S.

doi:10.1172/jci115063

Cited by 178 publications

(120 citation statements)

References 28 publications

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“…It is not yet clear why patients with STn-positive tumours should have a worse prognosis than those with STn-negative tumours. Sialomucins have been shown in colon cancer model systems to be important in metastasis (Bresalier et al, 1991), and most metastases of gastric cancer express STn (David et al, 1992). In addition, mucins bearing STn antigen can mediate inhibition of natural killer cell cytotoxicity, thereby providing a mechanism for immune escape (Ogata et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

Mucin-associated sialosyl-Tn antigen expression in gastric cancer correlates with an adverse outcome

Werther

Rivera-MacMurray²,

Bruckner³

et al. 1994

Br J Cancer

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The expression of sialosyl-Tn (STn) antigen was evaluated by immunohistochemistry in primary gastric cancers. Twenty-one of 31 (68%) gastric cancers expressed STn, regardless of tumour location, stage or histological type. Eighty-one per cent of patients with STn-positive tumours died of their disease or had recurrent cancer, compared with 20% of patients with STn-negative tumours (P < 0.002). STn may be a useful prognostic marker in patients with gastric cancer. Images Figure 1

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Section: Discussionmentioning

confidence: 99%

Mucin-associated sialosyl-Tn antigen expression in gastric cancer correlates with an adverse outcome

Werther

Rivera-MacMurray²,

Bruckner³

et al. 1994

Br J Cancer

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“…A previous study in athymic nude mice has reported that GalNAc␣-O-bn could significantly reduce liver colonization by the mucin-secreting variant LiM6 of colon carcinoma LS174T cells, which mainly expresses the mucin MUC2. 48 However, our previous work has shown that this GalNAc-␣-O-bn induced particular effects in the model of mucin-secreting HT-29 cells, specifically, i.e., an inhibition in the secretion of MUC5AC in the apical culture medium, and the disappearance of MUC1 at the apical membrane, these glycoproteins remaining accumulated inside the cells. 49 -51 In contrast, the basolateral glycoprotein E-cadherin was not affected (data not shown).…”

Section: Immunofluorescence Analysis Of the Distribution Of E-cadherimentioning

confidence: 92%

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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“…The mucin family of anti-adhesion molecules have been implicated in the biological behaviour and progression of several types of cancer (Bresalier et al, 1991;Gendler and Spicer, 1995). The mucin MUC-1, which is expressed at the apical cell surface of many normal secretory epithelial cells (Ho et al, 1993), contains an extra-cellular domain that extends above most other cell membrane-associated proteins (Hilkens et al, 1992;Hilkens et al, 1995).…”

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confidence: 99%

MUC-1 gene is associated with prostate cancer death: a 20-year follow-up of a population-based study in Sweden

et al. 2007

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Anti-adhesion mucins have proven to play an important part in the biology of several types of cancer. Therefore, we test the hypothesis that altered expression of MUC-1 is associated with prostate cancer progression. We retrieved archival tumour tissue from a population-based cohort of 195 men with localised prostate cancer (T1a-b, Nx, M0) that has been followed for up to 20 years with watchful waiting. Semi-automated, quantitative immunohistochemistry was undertaken to evaluate MUC-1 expression. We modelled prostate cancer-specific death as a function of MUC-1 levels accounting for age, Gleason grade and tumour extent, and calculated age-adjusted and multivariate adjusted hazard ratios (HR). Men that had tumours with an MUC-intensity lower or higher than normal tissue had a higher risk of dying in prostate cancer, independent of tumour extent and Gleason score (HR 5.1 and 4.5, respectively). Adjustment for Gleason grade and tumour stage did not alter the results. Men with a Gleason score X7 and MUC-1 deviating from the normal had a 17 (RR ¼ 17.1 95% confidence interval ¼ 2.3 -128) times higher risk to die in prostate cancer compared with men with Gleason score o7 and normal MUC-1 intensity. In summary, our data show that MUC-1 is an independent prognostic marker for prostate cancer death.

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Mucin production by human colonic carcinoma cells correlates with their metastatic potential in animal models of colon cancer metastasis.

Cited by 178 publications

References 28 publications

Mucin-associated sialosyl-Tn antigen expression in gastric cancer correlates with an adverse outcome

Mucin-associated sialosyl-Tn antigen expression in gastric cancer correlates with an adverse outcome

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

MUC-1 gene is associated with prostate cancer death: a 20-year follow-up of a population-based study in Sweden

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