CD66c is a novel marker for colorectal cancer stem cell isolation, and its silencing halts tumor growth in vivo

Marica Gemei, Peppino Mirabelli, Rosa Di Noto, Claudia Corbo, Antonino Iaccarino, Anna Zamboli, Giancarlo Troncone, Gennaro Galizia, Eva Lieto, Luigi Del Vecchio, Francesco Salvatore

Research output: Contribution to journalArticle

Abstract

Background: Despite the well recognized expression of the cell surface markers cluster of differentiation 44 (homing cell adhesion molecule) and CD133 (Prominin 1) on human colorectal cancer stem cells (CCSCs), these molecules do not appear to be effective targets for stem cell-directed therapies. Because the surface marker CD66c (also known as carcinoembryonic antigen-related cell adhesion molecule 6) has demonstrated promise as a therapeutic target in pancreatic malignancy, the authors evaluated its potential as a target for stem cell-directed treatment of colorectal cancer. 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 CD66cbright 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.

Original languageEnglish
Pages (from-to)729-738
Number of pages10
JournalCancer
Volume119
Issue number4
DOIs
Publication statusPublished - Feb 15 2013

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Keywords

  • carcinoembryonic antigen-related cell adhesion molecule 6
  • cluster of differentiation 66c
  • colon cancer
  • small-interfering RNA silencing
  • stem cell-directed therapy
  • stem cells

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Gemei, M., Mirabelli, P., Di Noto, R., Corbo, C., Iaccarino, A., Zamboli, A., Troncone, G., Galizia, G., Lieto, E., Del Vecchio, L., & Salvatore, F. (2013). CD66c is a novel marker for colorectal cancer stem cell isolation, and its silencing halts tumor growth in vivo. Cancer, 119(4), 729-738. https://doi.org/10.1002/cncr.27794