MULTICELLULAR SPHEROIDS AS AN IN-VITRO TUMOR-MODEL

Multicellular spheroids (MCS) have been used as an in vitro model syst em of micrometastases and avascular tumor regions for studying cell ad hesion-dependent resistance to cytotoxic drugs and possible reversal b y chemosensitizers and adhesion-reversing agents. Multicellular drug r esistance has been linked to limited accessibility of cell subpopulati ons, active drug efflux, quiescence of cells in deeper layers due to c ell contact inhibition and adverse microenvironmental conditions like acidic extracellular pH, hypoxia and nutritional depletion. The shortc omings of MCS as a tumor model include limited knowledge of the mechan isms leading to necrosis/apoptosis of core cells, the production of an extracellular matrix (ECM) by tumor cells instead of intratumoral nor mal cell populations and the complex relationship of MCS parameters li ke size, growth regulation, synthesis of ECM components and others on the origin and pretreatment of the tumor cells and specific culture co nditions. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.