Colon cancer stem cells resist antiangiogenesis therapy-induced apoptosis

Cancer Lett. 2013 Jan 28;328(2):226-34. doi: 10.1016/j.canlet.2012.08.036. Epub 2012 Sep 24.

Abstract

Antiangiogenesis is an efficient therapy for eliminating colon cancers, but because of recurrence it remains only palliative. We hypothesized that certain populations of tumor cells resist antiangiogenesis-induced apoptosis and explored the underlying mechanism. We demonstrated that the CD133(+) population of cells in colon cancer is resistant to anti-angiogenesis therapy. Additionally, we identified an anti-apoptotic signaling pathway responsible for this resistance involving PP2A, p38MAPK, MAPKAPK2, and Hsp27. Thus, this pathway may offer a new avenue to develop target therapy for colorectal cancer.

MeSH terms

  • AC133 Antigen
  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Antigens, CD / metabolism
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / pathology
  • Drug Resistance, Neoplasm
  • Glycoproteins / metabolism
  • HSP27 Heat-Shock Proteins / metabolism
  • Humans
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Mitogen-Activated Protein Kinases / metabolism
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / metabolism*
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / metabolism*
  • Peptides / metabolism
  • Protein Phosphatase 2 / metabolism
  • Signal Transduction / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • AC133 Antigen
  • Angiogenesis Inhibitors
  • Antigens, CD
  • Antineoplastic Agents
  • Glycoproteins
  • HSP27 Heat-Shock Proteins
  • PROM1 protein, human
  • Peptides
  • Prom1 protein, mouse
  • Mitogen-Activated Protein Kinases
  • Protein Phosphatase 2