Slow-cycling Therapy-Resistant Cancer Cells

Stem Cells Dev. 2012 Jul 1;21(10):1822-30. doi: 10.1089/scd.2011.0477. Epub 2011 Nov 11.

Abstract

Tumor recurrence after chemotherapy is a major cause of patient morbidity and mortality. Recurrences are thought to be secondary to small subsets of cancer cells that are better able to survive traditional forms of chemotherapy and thus drive tumor regrowth. The ability to isolate and better characterize these therapy-resistant cells is critical for the future development of targeted therapies aimed at achieving more robust and long-lasting responses. Using a novel application for the proliferation marker carboxyfluorescein diacetate, succinimidyl ester (CFSE), we have identified a population of slow-cycling, label-retaining tumor cells in both in vitro sphere cultures and in vivo xenograft models. Strikingly, label-retaining cells exhibit a multifold increase in ability to survive traditional forms of chemotherapy and reenter the cell cycle. Further, we demonstrate the innovative application of CFSE to live sort slow-cycling tumor cells and validate their chemoresistance and tumorigenic potential.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cell Line, Tumor
  • Cell Proliferation
  • Drug Resistance, Neoplasm*
  • Fluoresceins / chemistry
  • Fluoresceins / metabolism
  • Fluorescent Dyes / chemistry
  • Fluorescent Dyes / metabolism
  • Fluorouracil / administration & dosage
  • Humans
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Neoplasms, Experimental / drug therapy
  • Neoplasms, Experimental / pathology*
  • Organoplatinum Compounds / administration & dosage
  • Oxaliplatin
  • Succinimides / chemistry
  • Succinimides / metabolism
  • Xenograft Model Antitumor Assays

Substances

  • 5-(6)-carboxyfluorescein diacetate succinimidyl ester
  • Fluoresceins
  • Fluorescent Dyes
  • Organoplatinum Compounds
  • Succinimides
  • Oxaliplatin
  • Fluorouracil