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J Surg Oncol ; 107(7): 713-22, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23335066

ABSTRACT

BACKGROUND AND OBJECTIVES: MUC1 is over-expressed and aberrantly glycosylated in >60% of human pancreatic cancer (PC). Development of novel approaches for detection and/or targeting of MUC1 are critically needed and should be able to detect MUC1 on PC cells (including cancer stem cells) and in serum. METHODS: The sensitivity and specificity of the anti-MUC1 antibody, TAB 004, was determined. CSCs were assessed for MUC1 expression using TAB 004-FITC on in vitro PC cell lines, and on lineage(-) cells from in vivo tumors and human samples. Serum was assessed for shed MUC1 via the TAB 004 EIA. RESULTS: In vitro and in vivo, TAB 004 detected MUC1 on >95% of CSCs. Approximately, 80% of CSCs in patients displayed MUC1 expression as detected by TAB 004. Shed MUC1 was detected serum in mice with HPAF-II (MUC1(high) ) but not BxPC3 tumors (MUC1(low)). The TAB 004 EIA was able to accurately detect stage progression in PC patients. CONCLUSIONS: The TAB 004 antibody may be explored as a therapeutic targeting agent for CSCs in PC. The TAB 004 EIA detected circulating MUC1 in a stage-dependent manner in patients with PC and thus may be explored as a PC stage diagnostic biomarker.


Subject(s)
Adenocarcinoma/metabolism , Mucin-1/immunology , Mucin-1/isolation & purification , Neoplastic Stem Cells/immunology , Pancreatic Neoplasms/metabolism , AC133 Antigen , Adenocarcinoma/immunology , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Animals , Antibodies, Monoclonal/pharmacology , Antigens, CD/immunology , Blotting, Western , Enzyme-Linked Immunosorbent Assay , Female , Fluorescent Antibody Technique , Gene Expression Regulation, Neoplastic , Glycoproteins/immunology , Glycosylation , Humans , Immunoenzyme Techniques , Immunohistochemistry , Male , Mice , Mice, Inbred BALB C , Mice, Knockout , Mice, Nude , Mice, Transgenic , Middle Aged , Neoplasm Staging , Pancreatic Neoplasms/immunology , Pancreatic Neoplasms/pathology , Peptides/immunology , Sensitivity and Specificity , Up-Regulation
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