The use of a novel MUC1 antibody to identify cancer stem cells and circulating MUC1 in mice and patients with pancreatic cancer

J Surg Oncol. 2013 Jun;107(7):713-22. doi: 10.1002/jso.23316. Epub 2013 Jan 17.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen
  • Adenocarcinoma / immunology
  • Adenocarcinoma / metabolism*
  • 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
  • Mucin-1 / immunology*
  • Mucin-1 / isolation & purification*
  • Neoplasm Staging
  • Neoplastic Stem Cells / immunology*
  • Pancreatic Neoplasms / immunology
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology
  • Peptides / immunology
  • Sensitivity and Specificity
  • Up-Regulation

Substances

  • AC133 Antigen
  • Antibodies, Monoclonal
  • Antigens, CD
  • Glycoproteins
  • MUC1 protein, human
  • Mucin-1
  • Peptides
  • muc1 protein, mouse