Human colon cancer stem cells are enriched by insulin-like growth factor-1 and are sensitive to figitumumab

Cell Cycle. 2011 Jul 15;10(14):2331-8. doi: 10.4161/cc.10.14.16418. Epub 2011 Jul 15.


Cancer stem cells (CSCs) are recognized as contributors to cancer progression and therapeutic resistance in liquid and solid malignancies. We analyzed a panel of human colon cancer cell lines for CSC populations by side population and aldehyde dehydrogenase activity. IGF-1 enriches these putative colon CSC populations in a β-catenin-dependent manner. Chemical inhibition of Akt depletes SP cells, and conversely, the overexpression of a constitutively active mutant version of Akt is sufficient to enrich CSC populations. CP-751,871, a fully human antibody with specificity to the IGF-1 receptor, is currently being tested in clinical trials for a variety of solid tumors. CP-751,871 reduces CSC populations in colon cancer cell lines in vitro and reduces tumor growth in vivo. We have identified a novel role for IGF-1 in the enrichment of chemo-resistant CSC populations. Our results suggest that CP-751,871 has preferential activity against putative CSC populations and, therefore, may complement current standard chemotherapeutic regimens that target cycling cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Colonic Neoplasms / pathology*
  • Humans
  • Immunoglobulins, Intravenous
  • Insulin-Like Growth Factor I / pharmacology*
  • Mice
  • Mice, Nude
  • Neoplastic Stem Cells / cytology
  • Neoplastic Stem Cells / drug effects*
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Receptor, IGF Type 1 / antagonists & inhibitors
  • Receptor, IGF Type 1 / immunology
  • Receptor, IGF Type 1 / metabolism
  • Transplantation, Heterologous
  • beta Catenin / antagonists & inhibitors
  • beta Catenin / genetics
  • beta Catenin / metabolism


  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Immunoglobulins, Intravenous
  • RNA, Small Interfering
  • beta Catenin
  • Insulin-Like Growth Factor I
  • Receptor, IGF Type 1
  • Proto-Oncogene Proteins c-akt
  • figitumumab