Frequency Distribution Histograms of Oxygen Tensions in Multicell Spheroids

Abstract

By growing multicell spheroids microenvironmental conditions can be created for the cancer similar to those the cells are exposed to in solid tumors (Sutherland and Durand, 1976; Franko and Sutherland, 1979a; Carlsson et al., 1979). Since the tumor cells in spheroids are predominantly supplied by the diffusion of substrates from the surrounding growth medium into the spheroid, the location of cells within the spheroid is a critical determinant of the efficiency of the nutritive supply to the cells. Thus, the situation of the spheroid cells may be comparable to that of cells located in between nutritive vessels in a solid tumor being supplied by diffusion from substrates from the tumor capillaries. In both cases cells may be located beyond critical diffusion distances and may die due to a lack of nutrients. The development of necrosis both in many solid tumors and in the center of spheroids (Sutherland and Durand, 1976; Franko and Sutherland, 1979a) supports these considerations. The supply conditions in solid tumors are mainly determined by the blood flow through the vascular bed and by the density of the tumor capillaries (Vaupel, 1977; Mueller-Klieser et al., 1980), i.e. by the concentration of nutrients in the supplying vessels and by the geometrical conditions for the diffusion of the nutrients to the cells. The nutritive supply of cells in a spheroid depends on the concentration of the nutrients in the culture medium, on the spheroid diameter, and on the location of the cells with regard to the spheroid rim.