title: Monoclonal antibody CC188 binds a carbohydrate epitope expressed on the surface of both colorectal cancer stem cells and their differentiated progeny.
abstract: OBJECTIVE
  Recently, cancer stem cells (CSC), undifferentiated cancer progenitor cells, have been successfully isolated from colorectal tumors. Targeting both CSCs and differentiated, rapidly proliferating tumor cells with therapeutic drugs provides a focused strategy to treat cancer. In this study, we isolated the monoclonal antibody (mAb) CC188 and characterized the epitope recognized by mAb CC188, which is useful for developing biological reagents that target CSCs.
  
  
  METHODS
  We used a hybridoma technique to generate mAbs and an immunomagnetic method to isolate colon CSCs. We characterized mAb CC188 binding epitope and examined the epitope distribution in normal and tumor tissues, particularly in CSCs using tissue arrays and immunofluorescence staining method. We also evaluated the effect of mAb CC188 on invasiveness of NSY tumor cells.
  
  
  RESULTS
  mAb CC188 was generated and 98.9% (187 of 189 cases) of colon cancer were positively stained by mAb CC188. "+", "++," and "+++" staining were 25.9%, 28.6%, and 43.4%, respectively. The mAb CC188 binding epitope was identified as a carbohydrate, which was expressed on the surface of colon CSCs (CD133+), differentiated colon cancer cells (CD133-), and cells from various types of epithelial tumors. In contrast, the expression of the carbohydrate epitope was low in normal prostate muscle and pancreatic acinar cells, as well as in some normal epithelial cells of the breast duct, cervix, and skin. A functional study indicated that mAb CC188 suppressed the invasiveness of NSY tumor cells.
  
  
  CONCLUSIONS
  mAb CC188 selectively targets a carbohydrate epitope expressed on cancer cells, providing a viable method for specific tumor imaging and targeted therapy.
authors.affiliation: Department of Radiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA. xum@mir.wustl.edu
authors.forename: Mai
authors.initials: M
authors.lastname: Xu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
authors.forename: Yang
authors.initials: Y
authors.lastname: Xia
authors.forename: Samuel
authors.initials: S
authors.lastname: Achilefu
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity; D000951:Antigens, Neoplasm / Q000276:immunology*; D002241:Carbohydrates / Q000276:immunology*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000276:immunology*; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D018189:Immunomagnetic Separation; D009361:Neoplasm Invasiveness / Q000276:immunology; D014411:Neoplastic Stem Cells / Q000276:immunology*; D046888:Tissue Array Analysis
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D002241:Carbohydrates; D018985:Epitopes, B-Lymphocyte