Casciari J J, Sotirchos S V, Sutherland R M
Experimental Therapeutics Division, University of Rochester Cancer Center, NY 14627.
Cancer Res. 1988 Jul 15;48(14):3905-9.
In order to understand the role of glucose limitations in controlling multicellular tumor spheroid growth, knowledge of the glucose diffusion coefficient is essential. The effective diffusivity of glucose in spheroids of rodent and human tumor cell lines has been determined by measuring the efflux of tritium labeled L-glucose from spheroids with time. When the rapid and irreversible binding of L-glucose in spheroids is properly taken into account, measurements of the efflux of this diffusion tracer from spheroids into label-free medium can be correlated to the diffusion equation in order to obtain the effective glucose diffusivity in spheroids. Such measurements have been made in EMT6/Ro mouse mammary tumor spheroids as well as in spheroids derived from human colon carcinoma cells (HT29, CO112, and WiDr) and from human squamous carcinoma cells (CaSki and A431). EMT6/Ro spheroids have a glucose diffusivity of 1.1 x 10(-6) cm2/s, while glucose diffusion coefficients in the human cell spheroids studied vary from 5.5 x 10(-7) cm2/s to 2.3 x 10(-7) cm2/s. These values are low enough to suggest that significant gradients in glucose concentration may exist in spheroids and tumors. It is thus believed that these glucose diffusivities, as well as their variation with cell line, may have important implications for the role played by glucose in the growth and cellular heterogeneity of spheroids and tumors.
为了理解葡萄糖限制在控制多细胞肿瘤球体生长中的作用，了解葡萄糖扩散系数至关重要。通过测量氚标记的L-葡萄糖从球体随时间的流出量，已确定了葡萄糖在啮齿动物和人类肿瘤细胞系球体中的有效扩散率。当适当考虑L-葡萄糖在球体中的快速且不可逆结合时，这种扩散示踪剂从球体流入无标记培养基的流出量测量值可与扩散方程相关联，以获得球体中葡萄糖的有效扩散率。已在EMT6/Ro小鼠乳腺肿瘤球体以及源自人结肠癌细胞（HT29、CO112和WiDr）和人鳞状癌细胞（CaSki和A431）的球体中进行了此类测量。EMT6/Ro球体的葡萄糖扩散率为1.1×10^(-6) cm²/s，而所研究的人类细胞球体中的葡萄糖扩散系数在5.5×10^(-7) cm²/s至2.3×10^(-7) cm²/s之间变化。这些值足够低，表明球体和肿瘤中可能存在显著的葡萄糖浓度梯度。因此，人们认为这些葡萄糖扩散率及其随细胞系的变化，可能对葡萄糖在球体和肿瘤生长及细胞异质性中所起的作用具有重要意义。
