MUC1 expression in human prostate cancer cell lines and primary tumors

O’Connor, John C.; Julian, JoAnne; Lim, So Dug; Carson, Daniel D.

doi:10.1038/sj.pcan.4500762

Cited by 53 publications

(53 citation statements)

References 31 publications

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“…In a comparison between gene expression in primary and metastatic prostate cancer tissues, the MUC1 gene was not found to be differentially expressed (58). Using a MAb against a cytoplasmic epitope of MUC1, O'Connor et al (37) concluded that MUC1 expression was heterogeneous in both normal and malignant prostate epithelia. On the other hand, Arai et al (36) found a correlation between the levels of sialylated MUC1 and the histological grade and clinical stage of the prostate cancer using MAb MYE12, which detects sialylated MUC1.…”

Section: Discussionmentioning

confidence: 99%

“…Other studies, utilizing a single antibody against MUC1 extracellular epitopes, have shown an association between disease progression and MUC1 expression (33)(34)(35)(36). In a study utilizing an antibody to the MUC1 cytoplasmic tail, no association with disease progression was found (37). MUC1 overexpression is also associated with tumor angiogenesis in prostate cancer (38), and may be modulated by androgens and estrogens (39,40).…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

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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“…In prostate cancer, overexpression of MUC-1 in tissue has been correlated both with higher Gleason grade and advanced tumour stage (Kirschenbaum et al, 1999). One study has, furthermore, suggested that MUC-1 expression may predict prostate cancer recurrence after prostatectomy (Lapointe et al, 2004), although these results have been challenged by others (O'Connor et al, 2005;Zellweger et al, 2005).…”

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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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“…1A). MUC1 is a large transmembrane glycoprotein that is commonly expressed in a variety of epithelial tissues in the human body (15,16) where it hydrates the epithelia, enhances adhesion to neighboring cells, and provides a barrier to pathogenic invasion. Overexpression of MUC1 with reduced glycosylation is characteristic for prostate, breast, colon, lung, gastric, and pancreatic cancers (17,18), and clinical trials targeting the MUC1 marker in solid tumors with multivalent Ab-based drugs have produced promising results for metastatic breast and prostate cancers (19,20).…”

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confidence: 99%

Dynamic force spectroscopy of parallel individual Mucin1–antibody bonds

Sulchek

Friddle

Langry

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

165

215

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We used atomic force microscopy to measure the binding forces between Mucin1 (MUC1) peptide and a single-chain variable fragment (scFv) antibody selected from a scFv library screened against MUC1. This binding interaction is central to the design of molecules used for targeted delivery of radioimmunotherapeutic agents for prostate and breast cancer treatment. Our experiments separated the specific binding interaction from nonspecific interactions by tethering the antibody and MUC1 molecules to the atomic force microscope tip and sample surface with flexible polymer spacers. Rupture force magnitude and elastic characteristics of the spacers allowed identification of the rupture events corresponding to different numbers of interacting proteins. We used dynamic force spectroscopy to estimate the intermolecular potential widths and equivalent thermodynamic off rates for monovalent, bivalent, and trivalent interactions. Measured interaction potential parameters agree with the results of molecular docking simulation. Our results demonstrate that an increase of the interaction valency leads to a precipitous decline in the dissociation rate. Binding forces measured for monovalent and multivalent interactions match the predictions of a Markovian model for the strength of multiple uncorrelated bonds in a parallel configuration. Our approach is promising for comparison of the specific effects of molecular modifications as well as for determination of the best configuration of antibody-based multivalent targeting agents.atomic force microscopy ͉ multivalency ͉ radioimmunmotherapy ͉ binding affinity I nteractions between biological molecules drive a vast variety of cellular processes and span a wide range of strength and complexity. Multivalent interactions where several binding units combine to produce superior binding strength play an important role in adaptive immune response (1) and intercellular adhesion (2), as well as in the mechanism of action of many pharmaceuticals (3). Clinical researchers have used multivalency as an affinity-enhancing approach (4, 5) in a variety of immunotherapies and imaging techniques to target specific tissues (6, 7).Linking several molecules into a large multivalent binding construct also creates bulky agents that exhibit reduced tissue penetration and have a higher probability of accumulation in liver (8). Therefore, a better understanding of the multivalent binding is necessary for the creation of optimized agents that balance binding efficiency and molecular size. Quantitative characterization of multivalent interactions is also important for understanding the basic biophysics of complex molecular systems.The last decade saw an explosion of interaction force measurement techniques that allowed researchers to measure and apply molecular level stresses (9-11). Atomic force microscopy (AFM) probes ligand-receptor interactions by simply pulling off the ligand from the receptor using external force (12). Kinetic approaches to the binding force measurements, such as dynamic force spectroscopy ...

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MUC1 expression in human prostate cancer cell lines and primary tumors

Cited by 53 publications

References 31 publications

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

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

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

Dynamic force spectroscopy of parallel individual Mucin1–antibody bonds

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