Enrichment of breast cancer stem-like cells by growth on electrospun polycaprolactone-chitosan nanofiber scaffolds

Int J Nanomedicine. 2014 Feb 19:9:995-1003. doi: 10.2147/IJN.S55720. eCollection 2014.

Abstract

A small population of highly tumorigenic breast cancer cells has recently been identified. These cells, known as breast-cancer stem-like cells (BCSC), express markers similar to mammary stem cells, and are highly resistant to chemotherapy. Currently, study of BCSC is hampered by the inability to propagate these cells in tissue culture without inducing differentiation. Recently, it was reported that proliferation and differentiation can be modified by culturing cells on electrospun nanofibers. Here, we sought to characterize the chemoresistance and stem-like properties of breast cancer cell lines grown on nanofiber scaffolds. Cells cultured on three-dimensional templates of electrospun poly(ε-caprolactone)-chitosan nanofibers showed increases in mammary stem cell markers and in sphere-forming ability compared with cells cultured on polystyrene culture dishes. There was no increase in proliferation of stem cell populations, indicating that culture on nanofibers may inhibit differentiation of BCSC. The increase in stemness was accompanied by increases in resistance to docetaxel and doxorubicin. These data indicate that BCSC populations are enriched in cells cultured on electrospun poly(ε-caprolactone)-chitosan nanofibers, scaffolds that may provide a useful system to study BCSC and their response to anticancer drug treatment.

Keywords: breast cancer; chemoresistance; mammary stem cells; nanofibers; three-dimensional culture.

Publication types

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

MeSH terms

  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Culture Techniques / methods*
  • Cell Differentiation
  • Cell Line, Tumor
  • Cell Proliferation
  • Chitosan / chemistry
  • Docetaxel
  • Doxorubicin / pharmacology
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • MCF-7 Cells
  • Nanofibers / chemistry*
  • Nanofibers / ultrastructure
  • Nanomedicine
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology*
  • Polyesters / chemistry
  • Taxoids / pharmacology
  • Tissue Scaffolds / chemistry
  • Tumor Stem Cell Assay

Substances

  • Biomarkers, Tumor
  • Polyesters
  • Taxoids
  • Docetaxel
  • polycaprolactone
  • Doxorubicin
  • Chitosan