Monoclonal antibody BrE-3 participation in a multivariate prognostic model for infiltrating ductal carcinoma of the breast

Chan, Curtis M.; Baratta, Frank; Ozzello, Luciano; Ceriani, Roberto L.

doi:10.1007/bf00665966

Cited by 7 publications

(4 citation statements)

References 23 publications

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“…In addition, high levels of episialin and leukosialin expression make cells less susceptible to cytolysis, probably favoring survival of circulating tumor cells or leukocytes (van de Wiel-van Kemenade et al, 1993;Mcfarland et al, 1995). However, the literature is not clear about the relationship between overexpression of episialin in carcinoma cells and prognosis, probably because tumor architecture and cellular localization of episialin have not been unequivocally assessed in various studies (Chan et al, 1994;Mcguckin et al, 1995). Not only anti-adhesive effects can be mediated by membrane-associated mucins, but also adhesion to selectins (for reviews, see Shimizu and Shaw, 1993;Rosen and Bertozzi, 1994;McEver et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

A mechanism for inhibition of E-cadherin-mediated cell-cell adhesion by the membrane-associated mucin episialin/MUC1.

Wesseling

Valk

Hilkens

1996

MBoC

365

294

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Episialin (MUC1, PEM, EMA, CA15-3 antigen) is a sialylated, membrane-associated glycoprotein with an extended mucin-like ectodomain. This domain mainly consists of 30-90 homologous 20-amino acid repeats that are rich in 0-glycosylation sites (serines and threonines). It is likely that this part forms a polyproline ,B-turn helix. As a result, the ectodomain can protrude more than 200 nm above the cell surface, whereas most cell surface molecules do not exceed a length of 35 nm. Normally, episialin is present at the apical side of glandular epithelial cells. On carcinoma cells, however, it can be strongly overexpressed and it is often present over the entire cell surface. We have previously shown that episialin, if it is interspersed between adhesion molecules, nonspecifically reduces cell-cell and cell-extracellular matrix interactions in vitro and in vivo, presumably by steric hindrance caused by the extreme length and high density of the episialin molecules at the cell surface. To analyze the molecular mechanism for this anti-adhesion effect in more detail, we have now deleted an increasing number of repeats in the episialin cDNA and transfected the resulting mutants into murine L929 cells expressing the homophilic adhesion molecule E-cadherin. Here we show that the length of episialin is the dominant factor that determines the inhibition of E-cadherin-mediated cell-cell interactions. For the anti-adhesive effect mediated by the full length episialin, charge repulsion by negatively charged sialylated 0-linked glycans is far less important.

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Section: Discussionmentioning

confidence: 99%

A mechanism for inhibition of E-cadherin-mediated cell-cell adhesion by the membrane-associated mucin episialin/MUC1.

Wesseling

Valk

Hilkens

1996

MBoC

365

294

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“…Seven mouse MAbs were chosen to evaluate MUC1 epitopes: B27.29, EMA, BC2, NCL-MUC1 Core, HMFG-1, BrE-3 and SM3 (Table I). With the exception of BrE-3, all of these MAbs were characterized extensively in the 1998 Workshop on MUC1 MAbs (42); in vitro and in vivo binding of BrE-3 has been described elsewhere (19,22,23,27,(43)(44)(45). MAb characterization included comparison for core peptide epitopes (46), VNTR affinity (47), effect of glycosylation on binding to VNTR (48), ability to bind to highly glycosylated (49) and hypoglycosylated cell lines (50) and binding to normal MUC1-expressing tissues (breast, small intestine, colon) (51).…”

Section: Methodsmentioning

confidence: 99%

“…Higher expression of aberrant forms of the MUC1 glycoprotein have been observed in a number of cancers (15)(16)(17)(18)(19)(20). Expression of MUC1 epitopes with reduced branching of O-glycans has been observed in breast cancer tissue (18,21) and was reflected by increased staining with MAbs recognizing hypoglycosylated MUC1 (17,20,(22)(23)(24)(25)(26)(27). However, not all cancers express high levels of hypoglycosylated MUC1 epitopes and cancer progression is not always associated with this MUC1 form (11,28,29).…”

Section: Introductionmentioning

confidence: 99%

Characterization of MUC1 glycoprotein on prostate cancer for selection of targeting molecules

Burke

Gregg²,

Bakhtiar³

et al. 2006

Int J Oncol

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Abstract. MUC1 glycoprotein that is overexpressed in aberrant forms in epithelial cancers has been used for diagnosis, staging and therapy. As normal prostate and prostate cancer tissues express MUC1, it represents a potential target, but MUC1 epitopes specific to prostate cancer have not been well characterized. In order to assess MUC1 epitopes in prostate cancer, and their correlation with Gleason grades, binding of 7 wellcharacterized anti-MUC1 monoclonal antibodies (MAbs) (BrE-3, SM3, BC2, EMA, B27.29, HMFG-1 and NCL MUC1 core), were studied on a prostate tissue microarray. This microarray contained 197 prostate tissue cores representing: i) normal/benign prostate; ii) prostatic intraepithelial neoplasia and Gleason grades 1 and 2; and iii) Gleason grades 3-5. These MAbs bind the MUC1 extracellular domain, but have variable sensitivity to MUC1 glycosylation. To further characterize the effect of glycosylation on their binding, MAb reactivities with unglycosylated MUC1 core peptide and breast and prostate cancer cell lysates were compared. These studies demonstrated strong binding of BrE-3, BC2 and EMA to the peptide core and recognition by BrE-3, SM3, BC2 and EMA of hypoglycosylated MUC1. The results for the microarray indicated that higher Gleason grades were associated with markedly increased cellular staining by MAbs that preferentially recognize less glycosylated MUC1 p<0.001; SM3, p<0.004; EMA, p=0.009; and BC2, p<0.001

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“…In practice, it is not easy to distinguish the two types of study, and we have included a few studies with aims that were somewhat ambiguous. For example, the study of Cooke and colleagues 126 was included, which examined the impact of adding HER2 to the Nottingham Prognostic Index (NPI), and the study of Chan and colleagues, 127 in which the monoclonal antibody BRE-3 was explored in the context of an overall prognostic model. For inclusion, a study had to consider at least one of the end-points of death, cancer death or recurrence of disease in newly diagnosed patients, and these were the only outcomes that we considered.…”

Section: Introductionmentioning

confidence: 99%

Cost-effectiveness of using prognostic information to select women with breast cancer for adjuvant systemic therapy

Williams

Brunskill²,

Altman³

et al. 2006

Health Technol Assess

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Outputs from the framework constructed using the methods described here have the potential to be useful for clinicians, attempting to determine whether net benefits can be obtained from administering adjuvant therapy for any presenting woman; and also for policy makers, who must be able to determine the total costs and outcomes associated with different prognosis based treatment protocols as compared with more conventional treat all or treat none policies. A risk table format enabling clinicians to look up a patient's prognostic factors to determine the likely benefits (survival and quality-adjusted survival) from administering therapy may be helpful. For policy makers, it was demonstrated that the model's output could be used to evaluate the cost-effectiveness of different treatment protocols based upon prognostic information. The framework should also be valuable in evaluating the likely impact and cost-effectiveness of new potential prognostic factors and adjuvant therapies.

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Monoclonal antibody BrE-3 participation in a multivariate prognostic model for infiltrating ductal carcinoma of the breast

Cited by 7 publications

References 23 publications

A mechanism for inhibition of E-cadherin-mediated cell-cell adhesion by the membrane-associated mucin episialin/MUC1.

A mechanism for inhibition of E-cadherin-mediated cell-cell adhesion by the membrane-associated mucin episialin/MUC1.

Characterization of MUC1 glycoprotein on prostate cancer for selection of targeting molecules

Cost-effectiveness of using prognostic information to select women with breast cancer for adjuvant systemic therapy

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