Distinctive alterations of invasiveness, drug resistance and cell-cell organization in 3D-cultures of MCF-7, a human breast cancer cell line, and its multidrug resistant variant

Clin Exp Metastasis. 2002;19(2):161-8. doi: 10.1023/a:1014594825502.


Growth of human tumor cells as three-dimensional (3D) multicellular spheroids modifies their invasive properties. Here we study the differences in the biological features of MCF-7, a human breast cancer cell line, and its multidrug resistant variant (MDR-MCF-7) cultured as spheroids or as monolayers. Three-dimensional culture decreased the proliferative rate of both cell lines, reduced the drug sensitivity of MCF-7 cells and did not affect the resistance of MDR-MCF-7 cells. Transmission electron microscopic studies and intercellular junctions labeling showed that MCF-7 spheroids had a junctional system involving E-cadherin, tight-junctions and desmosomes. In MDR-MCF-7 cell spheroids, cell cohesion was mostly due to membrane interdigitations. MDR-MCF-7 cells, but not their parental counterpart, displayed a higher invasive potential when cultured as spheroids, as shown in the Boyden chamber assay. 3D-induced invasiveness was correlated with serine protease and plasminogen activator (PA) secretion. MCF-7 cells did not show any tendency to invade, whatever the mode of culture. These results show that 3D-cultures as spheroids distinctively altered structural features of parental and MDR-MCF-7 cells. In MCF-7 cells, 3D-culture increased cell-cell contacts and drug resistance; in MDR-MCF-7 cells, it induced invasive properties.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Antibiotics, Antineoplastic / pharmacology
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cadherins / metabolism
  • Caseins / metabolism
  • Cell Movement / physiology*
  • Collagen / metabolism
  • Doxorubicin / pharmacology
  • Drug Combinations
  • Drug Resistance, Multiple / physiology*
  • Drug Resistance, Neoplasm / physiology*
  • Female
  • Gelatin / metabolism
  • Humans
  • Intercellular Junctions / physiology*
  • Laminin / metabolism
  • Matrix Metalloproteinases / metabolism
  • Microscopy, Electron
  • Neoplasm Metastasis
  • Plasminogen Activators / metabolism
  • Proteoglycans / metabolism
  • Spheroids, Cellular / metabolism
  • Spheroids, Cellular / pathology*
  • Tumor Cells, Cultured / drug effects


  • Antibiotics, Antineoplastic
  • Cadherins
  • Caseins
  • Drug Combinations
  • Laminin
  • Proteoglycans
  • matrigel
  • Doxorubicin
  • Gelatin
  • Collagen
  • Plasminogen Activators
  • Matrix Metalloproteinases