The AC133 Epitope, but not the CD133 Protein, Is Lost upon Cancer Stem Cell Differentiation英文文献.pdfVIP

Tumor and Stem Cell Biology Cancer Research The AC133 Epitope, but not the CD133 Protein, Is Lost upon Cancer Stem Cell Differentiation 1 1 1 3 Kristel Kemper , Martin R. Sprick , Martijn de Bree , Alessandro Scopelliti , Louis Vermeulen1 4 2 2 , Maarten Hoek , Jurrit Zeilstra , Steven T. Pals , Huseyin Mehmet4 3 1 , Giorgio Stassi , and Jan Paul Medema Abstract Colon cancer stem cells (CSC) can be identified with AC133, an antibody that detects an epitope on CD133. However, recent evidence suggests that expression of CD133 is not restricted to CSCs, but is also expressed on differentiated tumor cells. Intriguingly, we observed that detection of the AC133 epitope on the cell surface de- creased upon differentiation of CSC in a manner that correlated with loss of clonogenicity. However, this event did not coincide with a change in CD133 promoter activity, mRNA, splice variant, protein expression, or even cell surface expression of CD133. In contrast, we noted that with CSC differentiation, a change occured in CD133 glycosylation. Thus, AC133 may detect a glycosylated epitope, or differential glycosylation may cause CD133 to be retained inside the cell. We found that AC133 could effectively detect CD133 glycosylation mutants or bacterially expressed unglycosylated CD133. Moreover, cell surface biotinyla