Spatial organization of three-dimensional cocultures of adriamycin-sensitive and -resistant human breast cancer MCF-7 cells.
Genetic and cellular heterogeneity is one of mechanisms involved in increasing tumour aggressiveness during neoplastic progression. Development of drug-resistant tumour cell subpopulations is a major problem in clinical oncology. Multi-drug resistant tumour cells survive when exposed to cytotoxic agents. Here, we studied in a three-dimensional (3D) coculture system, called "ex vivo nodules", how drug-resistant and sensitive tumour cells settle down in a 3D space. For this, we cocultured adriamycin-sensitive (MCF-7S) and -resistant (MCF-7R) human breast cancer cells in long term nodules. We showed that both types of cells are able to grow separately or in coculture until five weeks in spheroidal forms. MCF-7R cells did not loose their multi-drug resistance when cultured in nodules as measured by RT-PCR. Curiously, the exterior aspects of mixed (MCF-7S/ MCF-7R) nodules and MCF-7R nodules were similar whereas MCF-7S nodules were completely different. Nevertheless, morphologically these three nodule types were distinct, in particular in their density. Immunostaining showed that in mixed nodules, MCF-7R cells were arranged at the periphery, whereas the MCF-7S cells are in the central part of the nodules. Even if the mechanism of this arrangement remained unclear, this work shows that three-dimensional cell culture is well adapted to the study of the relationships between adhesion mechanisms and drug-resistance.
Starzec
A
A
Laboratoire de Pharmacologie, UPRES 2360, Université Paris 13, 74, rue Marcel-Cachin, F-93017 Bobigny Cedex, France.
Briane
D
D
Kraemer
M
M
Kouyoumdjian
J-C
JC
Moretti
J-L
JL
Beaupain
R
R
Oudar
O
O
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis / Q000235:genetics / Q000276:immunology; D017209:Apoptosis; D001943:Breast Neoplasms / Q000473:pathology; D002454:Cell Differentiation; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D018920:Coculture Techniques / Q000379:methods*; D004317:Doxorubicin / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling / Q000379:methods; D007211:Indoles / Q000737:chemistry; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D012313:RNA / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D001613:beta 2-Microglobulin / Q000032:analysis / Q000235:genetics
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007211:Indoles; D001613:beta 2-Microglobulin; C007293:DAPI; D012313:RNA; D004317:Doxorubicin