Size-Dependent Oxygenation and Energy Status in Multicellular Tumor Spheroids

Multicellular tumor spheroids show numerous analogies to tumor microregions in vivo, such as the development of central necrosis at a certain spheroid size (for reviews see: Mueller-Klieser, 1987; Sutherland, 1988). The histological structure of the cell aggregates suggests that diffusion limitation of oxygen or nutrients in spheroids may cause cell death in the innermost parts of the spheroids. However, measurements with oxygen-sensitive microelectrodes are indicative of necrosis arising in the presence of relatively high oxygen tension (PO2) values, as they were found in normal tissue (Carlsson and Acker, 1985; Mueller-Klieser et al., 1986). Although still controversial in literature, rec…