Evidence for a Major Role of Glucose in Controlling Developmnet of Necrosis in EMT6/RO Multicell, Tumor Spheroids
Multicell tumor spheroids show many features of tumors in vivo such as saturation of growth, induction of quiescent cells (Freyer and Sutherland, 1980; Bauer et al., 1981) and development of necrosis (Sutherland and Durand, 1976; Franko and Sutherland, 1979b; Carlsson et al., 1979). These effects may be attributed to limited penetration of metabolites into the spheroid due to cellular consumption and due to restricted diffusion as the spheroid increases in size (Mueller-Klieser and Sutherland, 1981b). Many investigations of cells in vitro and in experimental tumors in vivo (Vaupel, 1980) have indicated that oxygen plays a decisive role in the control of the metabolism and the viability of cancer cells. It has also been demonstrated in spheroids that the thickness of the viable rim surrounding the necrotic center depends on the oxygen concentration in the culture medium (Franko and Sutherland, 1979a). Thus, oxygen can be a critical determinant for the development of necrosis in multicell tumor spheroids. Recent measurements, however, of pO2 values in spheroids using oxygen sensitive microelectrodes (Mueller-Klieser and Sutherland, 1981b) have demonstrated that necrosis may develop at different levels of oxygen tensions as the spheroids increase in size. This indicates that additional factors other than oxygen may also be involved in the control of cell death in spheroids. The present study was undertaken to investigate the influence of oxygen and glucose concentrations in the culture medium on the thickness of the viable rim and on the oxygen tensions in EMT6/Ro spheroids.
KeywordsOxygen Tension Tumor Spheroid Central Plateau Spinner Flask Controlling Development
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