Document Detail


Characterization of MUC1 glycoprotein on prostate cancer for selection of targeting molecules.
MedLine Citation:
PMID:  16773184     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 well-characterized 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 (BrE-3, p<0.001; SM3, p<0.004; EMA, p=0.009; and BC2, p<0.001). Staining by MAbs that bind preferentially to hyperglycosylated MUC1 (B27.29, p=0.33; HMFG-1, p=0.89; and NCL MUC1 core, p=0.96) did not correlate with Gleason grade. These results demonstrated that hypoglycosylated MUC1 expression increased with Gleason grade, thus supporting the targeting of hypoglycosylated MUC1 epitopes in prostate cancer for more specific imaging and therapy applications.
Authors:
Patricia A Burke; Jeffrey P Gregg; Brandon Bakhtiar; Laurel A Beckett; Gerald L Denardo; Huguette Albrecht; Ralph W De Vere White; Sally J De Nardo
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  International journal of oncology     Volume:  29     ISSN:  1019-6439     ISO Abbreviation:  Int. J. Oncol.     Publication Date:  2006 Jul 
Date Detail:
Created Date:  2006-06-14     Completed Date:  2007-08-03     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  9306042     Medline TA:  Int J Oncol     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  49-55     Citation Subset:  IM    
Affiliation:
Radiodiagnosis & Therapy, Internal Medicine, University of California at Davis, Sacramento Medical Center, 95816, USA.
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MeSH Terms
Descriptor/Qualifier:
Antibodies, Monoclonal / immunology
Antigens, Neoplasm / analysis,  immunology*
Cell Line, Tumor
Epitope Mapping*
Female
Glycosylation
Humans
Immunohistochemistry
Male
Mucin-1
Mucins / analysis,  immunology*
Prostatic Neoplasms / immunology*
Protein Processing, Post-Translational
Tissue Array Analysis
Tumor Markers, Biological / analysis*,  immunology
Grant Support
ID/Acronym/Agency:
P01 CA47829/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antigens, Neoplasm; 0/MUC1 protein, human; 0/Mucin-1; 0/Mucins; 0/Tumor Markers, Biological

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