Evidence of drug-response heterogeneity rapidly generated from a single cancer cell

Oncotarget. 2017 Jun 20;8(25):41113-41124. doi: 10.18632/oncotarget.17064.

Abstract

One cancer cell line is believed to be composed of numerous clones with different drug sensitivity. We sought to investigate the difference of drug-response pattern in clones from a cell line or from a single cell. We showed that 22 clones derived from 4T1 cells were drastically different from each other with respect to drug-response pattern against 11 anticancer drugs and expression profile of 19 genes associated with drug resistance or sensitivity. Similar results were obtained using daughter clones derived from a single 4T1 cell. Each daughter clone showed distinct drug-response pattern and gene expression profile. Similar results were also obtained using Bcap37 cells. We conclude that a single cancer cell can rapidly produce a population of cells with high heterogeneity of drug response and the acquisition of drug-response heterogeneity is random.

Keywords: cancer; drug-response; heterogeneity.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Clone Cells / drug effects*
  • Clone Cells / metabolism
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / genetics
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Mice
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Prohibitins
  • Single-Cell Analysis / methods*

Substances

  • Antineoplastic Agents
  • PHB2 protein, human
  • Phb2 protein, mouse
  • Prohibitins