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Magic Marker Mystery: Why Does Antibody AC133 So Specifically Recognize Stem Cells?
Author(s) -
Cooper Douglas N. W.,
Buselli Monica,
Castellanos Elizabeth,
Enerio Shiena T.,
Murti Akikta D.,
Reed Kimberli D.,
Wong Alyssa M.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.lb116
Subject(s) - stem cell , epitope , cancer stem cell , biology , microbiology and biotechnology , monoclonal antibody , antibody , stem cell marker , chemistry , immunology
Highly specific markers that distinguish stem from other cell types are critical tools for isolating stem cells, assaying their purity and functional status, and potentially targeting cancer stem cells for destruction. One of the most widely used markers for normal and cancer stem cells is a plasma membrane protein of unknown function, CD133. However, most antibodies to CD133 also recognize some non‐stem cell types. By contrast, the monoclonal antibody, AC133, seems to only recognize a subset of CD133 uniquely expressed on stem cells. Such specificity suggests a functionally role for this epitope in stem cell biology. Our aim has been to identify what epitope variation on CD133 makes AC133 so precise in identifying stem cells: e.g. splice variation in the CD133 protein sequence, post‐translational modification, or alternative conformation. Suspecting that tyrosine sulfation, a modification increasingly recognized on cell surface and extracellular proteins, might be involved, we tested the effect of sodium chlorate, a competitive inhibitor of sulfation, on CD133 expression in culture cells. 30mM chlorate blocked CD133 recognition by both AC133 and a specific anti‐sulfotyrosine antibody, indicating that tyrosine sulfation is a critical feature of the epitope recognized by AC133. We are now seeking other features of this epitope, its location on CD133, and its significance for stem cell physiology.