Cell culture as spheroids: an approach to multicellular resistance

Cells cultured as spheroids present an heterogeneity similar to that of tumours in vivo. In the spheroid peripheral layers, cells are proliferating, deeper cells are non-cycling, when in the aggregate centre, cells form often a necrotic core. A multicellular resistance is related on the cell contact to other cells or to the extracellular matrix. The mechanism of this resistance remains unknown. It seems to be linked to the spheroid centre hypoxia, quiescence of a large fraction of the cell population and to the apoptose inhibition. The "classical" or "unicellular" mechanisms of resistance, as mdr1, MRP, can coexist but are not responsible of this type of resistance. This culture model is a good opportunity to study a resistance which looks close to the patient tumour resistance. A new class of therapeutic molecules appears that can reverse multicellular resistance, inhibit tumours growth and preclude metastases. The mechanism of action of this new pharmacological class is the disruption of the cell adhesion forces.