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.
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.
dit Faute
Muriel Affoué
MA
UMR 147 CNRS, Institut Curie, Paris, France.
Laurent
Luc
L
Ploton
Dominique
D
Poupon
Marie-France
MF
Jardillier
Jean-Claude
JC
Bobichon
Hélène
H
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D015820:Cadherins / Q000378:metabolism; D002364:Caseins / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D003094:Collagen / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology; D004338:Drug Combinations; D018432:Drug Resistance, Multiple / Q000502:physiology*; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D005260:Female; D005780:Gelatin / Q000378:metabolism; D006801:Humans; D007365:Intercellular Junctions / Q000502:physiology*; D007797:Laminin / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008854:Microscopy, Electron; D009362:Neoplasm Metastasis; D010960:Plasminogen Activators / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D018874:Spheroids, Cellular / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000903:Antibiotics, Antineoplastic; D015820:Cadherins; D002364:Caseins; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D004317:Doxorubicin; D005780:Gelatin; D003094:Collagen; D010960:Plasminogen Activators; D020782:Matrix Metalloproteinases