Spatial organization of three-dimensional cocultures of XXXX -sensitive and -resistant @entity1 @entity0 MCF-7 cells.

@entity5 @entity1 @entity632 @entity0
Genetic and cellular heterogeneity is one of mechanisms involved in increasing @entity5 during @entity5 progression. Development of drug-resistant @entity5 cell subpopulations is a major problem in clinical oncology. Multi-drug resistant @entity5 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 @entity5 cells settle down in a 3D space. For this, we cocultured @entity632 -sensitive (MCF-7S) and -resistant (MCF-7R) @entity1 @entity0 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.
