Breast Cancer Spheroids Reveal a Differential Cancer Stem Cell Response to Chemotherapeutic Treatment

Sci Rep. 2017 Sep 4;7(1):10382. doi: 10.1038/s41598-017-10863-4.


An abnormal multicellular architecture is a defining characteristic of breast cancer and, yet, most in vitro tumor models fail to recapitulate this architecture or accurately predict in vivo cellular responses to therapeutics. The efficacy of two front-line chemotherapeutic agents (paclitaxel and cisplatin) are described within three distinct in vitro models employing the triple-negative basal breast cancer cell line MDA-MB-231 and the luminal breast cancer cell line MCF7: a) a 3D collagen embedded multicellular spheroid tumor model, which reflects the architecture and cellular heterogeneity of tumors in vivo; b) a 3D collagen model with a single cell-type diffusely embedded; and c) a 2D monolayer. The MDA-MB-231 embedded spheroid tumor model exhibited the most robust response to chemotherapeutic treatment, and possessed the greatest cancer stem cell (CSC) content. CSC-related genes are elevated across all MDA-MB-231 in vitro models following paclitaxel treatment, indicating that paclitaxel enrichment of chemoresistant CSCs is less dependent on microenvironmental tumor structure, while cisplatin showed a more context-dependent response. In the MCF7 cell models a context-dependent response is observed with paclitaxel treatment increasing the CSC related genes in the 2D monolayer and 3D diffuse models while cisplatin treatment afforded an increase in ALDH1A3 expression in all three models.

Publication types

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

MeSH terms

  • Aldehyde Oxidoreductases / genetics*
  • Antineoplastic Agents / pharmacology*
  • Breast Neoplasms / classification
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cisplatin / pharmacology
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • MCF-7 Cells
  • Neoplastic Stem Cells / cytology*
  • Neoplastic Stem Cells / drug effects
  • Paclitaxel / pharmacology
  • Spheroids, Cellular / cytology*
  • Spheroids, Cellular / drug effects
  • Treatment Outcome
  • Tumor Microenvironment / drug effects
  • Up-Regulation


  • Antineoplastic Agents
  • Aldehyde Oxidoreductases
  • aldehyde dehydrogenase (NAD(P)+)
  • Paclitaxel
  • Cisplatin