RESUMEN
IMPACT STATEMENT: Three dimensional in vitro cell culture systems better reflect the native structural architecture of tissues and are attractive to investigate cancer cell sensitivity to drugs. We have developed and compared several metastatic melanoma (MM) models cultured as a monolayer (2D) and cocultured on three dimensional (3D) dermal equivalents with fibroblasts to better unravel factors modulating cell sensitivity to vemurafenib, a BRAF inhibitor. The heterotypic 3D melanoma model we have established summarizes paracrine signalization by stromal cells and type I collagen matrix, mimicking the natural microenvironment of cutaneous MM, and allows for the identification of potent sensitive melanoma cells to the drug. This model could be a powerful tool for predicting drug efficiency.
Asunto(s)
Técnicas de Cocultivo , Melanoma/patología , Vemurafenib/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Medios de Cultivo Condicionados/farmacología , Dermis/patología , Fibroblastos/efectos de los fármacos , Humanos , Metástasis de la Neoplasia , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas B-raf/antagonistas & inhibidores , Proteínas Proto-Oncogénicas B-raf/metabolismo , Transducción de Señal/efectos de los fármacos , Solubilidad , Microambiente Tumoral/efectos de los fármacosRESUMEN
Biomedical applications often require to sort cells according to their physical properties, such as size, density or deformability. In recent years, microfluidics has provided a variety of tools to sort micro-objects. We present here a simple microfluidic device consisting of a channel containing a semi-cylindrical obstacle against which capsules are squeezed by the flow, followed by a diverging chamber where streamlines separate. We demonstrate that this basic system is capable of sorting elastic microcapsules according to their size at low flow strength, and according to the stiffness of their membrane at high flow strength. Contrary to most existing sorting devices, we show that the present one is very sensitive and capable of discriminating between capsules with differences in membrane elasticity of order unity.