Cell Cycle-Dependent Variation of a CD133 Epitope in Human Embryonic Stem Cell, Colon Cancer, and Melanoma Cell Lines

Tumor Development Program, Cancer Research Center, Burnham Institute for Medical Research, La Jolla, California 92035, USA.
Cancer Research (Impact Factor: 9.33). 11/2008; 68(19):7882-6. DOI: 10.1158/0008-5472.CAN-08-0723
Source: PubMed


CD133 (Prominin1) is a pentaspan transmembrane glycoprotein expressed in several stem cell populations and cancers. Reactivity with an antibody (AC133) to a glycoslyated form of CD133 has been widely used for the enrichment of cells with tumor-initiating activity in xenograph transplantation assays. We have found by fluorescence-activated cell sorting that increased AC133 reactivity in human embryonic stem cells, colon cancer, and melanoma cells is correlated with increased DNA content and, reciprocally, that the least reactive cells are in the G(1)-G(0) portion of the cell cycle. Continued cultivation of cells sorted on the basis of high and low AC133 reactivity results in a normalization of the cell reactivity profiles, indicating that cells with low AC133 reactivity can generate highly reactive cells as they resume proliferation. The association of AC133 with actively cycling cells may contribute to the basis for enrichment for tumor-initiating activity.

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    • "Some research have shown that the necessity of β-Catenin for self-renewal of both normal hematopoietic stem cells and Table1. Cancer stem marker and their distribution Marker Tumor type Marker Tumor type CD133 Brain[85] Prostate [86] Pancreas [ 87] Melanoma [88] Colon [88] Liver [89] Lung [19] Ovary [90] ALDH Breast [91] Lung [92] Head and neck [25] Colon [93] Liver [17] Pancreas [94] Gastric [95] Prostate [96] CD44 Colon [97] Breast [8] Prostate [13] Pancreatic [98] ABCB5 Melanoma [99] ABCG2 Pancreas [100] Lung [101] Limbal epithelium [102] Brain [103] prostate [104] Liver [105] Ovarian [106] Retinoblastoma [107] CD90 T-acute lymphoblastic leukemia [108] Gliomas [109] Liver [110] New therapies to target cancer stem cells 344 Am J Cancer Res 2012;2(3):340-356 "
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    • "This may be associated with the higher histological grading of GBM, thus supporting studies that suggest CD133 expression can be used as a prognostic factor [3] though CD133 did not achieve prognostic significance in our study. It is possible that not all of the CD133+ cells counted will have been glioma CSC’s with positive staining also depending upon the oxygen concentration and expression of the glycosylated AC133 epitope at different stages of the cell cycle [5, 24, 32]. "
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    • "A number of important regulators and pathways have been implicated in CSC biology and CD133 expression: mTOR, Wnt/β-catenin [42], PI3K-AKT [8, 13], reactive oxygen species-HIF1a pathway [43], Oct4 [9], and CXCR4 [35, 37]. Similar to embryonic stem cells, CD133+ colon cancer cells or melanoma expression are mostly found in the G1/G0 portion of the cell cycle [36]. CD133 expression is due to the lack of CpG island methylation [44, 45]. "
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