Abstract | BACKGROUND: METHODS: First, the authors characterized CD66c expression by flow cytometry and immunohistochemistry in colon cancer samples and in normal colon tissues. Then, the coexpression of CD66c and CD133 was evaluated on putative CCSCs. CD66c expression also was measured in stem cell-enriched colon spheres. Finally, the effects of small-interfering RNA-mediated CD66c silencing on the in vitro and in vivo growth of Caco2 colon cancer cells were evaluated. RESULTS: CD66c expression was significantly higher in colon cancers than in contiguous normal colon tissues and paralleled cancer stage. CD66c was absent in CD133-positive cells that were isolated from normal colon, whereas its expression was brightest (CD66c(bright) ) in CD133-positive cells from colon cancer samples. In vitro experiments demonstrated that colon spheres were considerably enriched in a CD66c(bright) population in a fashion comparable to the enrichment observed in fresh liver metastases. In vitro proliferation and clonogenic potential were hampered when CD66c was silenced in Caco2 cells. Finally, in vivo xenograft experiments demonstrated that CD66c silencing almost completely abrogated the tumorigenic potential of Caco2 cells. CONCLUSIONS: CD66c(bright) expression was associated with colon cancer stem cells and CD66c silencing blocked tumor growth, thereby opening the way to a potential new treatment for colon cancer.
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Authors | Marica Gemei, Peppino Mirabelli, Rosa Di Noto, Claudia Corbo, Antonino Iaccarino, Anna Zamboli, Giancarlo Troncone, Gennaro Galizia, Eva Lieto, Luigi Del Vecchio, Francesco Salvatore |
Journal | Cancer
(Cancer)
Vol. 119
Issue 4
Pg. 729-38
(Feb 15 2013)
ISSN: 1097-0142 [Electronic] United States |
PMID | 23027178
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2012 American Cancer Society. |
Chemical References |
- AC133 Antigen
- Antigens, CD
- Biomarkers, Tumor
- CEACAM6 protein, human
- Cell Adhesion Molecules
- GPI-Linked Proteins
- Glycoproteins
- PROM1 protein, human
- Peptides
- Prom1 protein, mouse
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Topics |
- AC133 Antigen
- Animals
- Antigens, CD
(genetics, metabolism)
- Biomarkers, Tumor
(metabolism)
- Caco-2 Cells
- Cell Adhesion Molecules
(genetics, metabolism)
- Cell Separation
(methods)
- Colon
(metabolism)
- Colorectal Neoplasms
(genetics, metabolism, pathology)
- Female
- GPI-Linked Proteins
(genetics, metabolism)
- Gene Silencing
- Glycoproteins
(metabolism)
- Humans
- Male
- Mice
- Mice, Nude
- Neoplastic Stem Cells
(metabolism)
- Peptides
(metabolism)
- Reference Values
- Xenograft Model Antitumor Assays
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