ABSTRACT
Multicellular spheroids are spherical aggregrates of tumor cells, with radial proliferation gradients and central necrosis, and are suitable as models in studies of the microenvironment in tumor nodules. The microenvironment in cellular spheroids is characterized by the cell density; the extracellular matrix; the local pO2 and pH conditions; starvation zones regarding glucose, amino acids, and other nutrients; and the accumulation of catabolic products. The chapter discusses the probable interconnections of pO2 and pH with growth, angiogenesis factor production, and, to some degree, the effects of radiation on the pO2 values in spheroids. Multicellular spheroids have radial pO2-gradients due to oxygen consumption, and radial pH-gradients mainly caused by glycolytic breakdown of glucose to lactate. The HT-29 spheroids produced factors that stimulated thymidine incorporation in endothelial cells, and the stimulation varied with pO2. Spheroids possess a heterogeneous cellular organization in conjunction with radial proliferation gradients and central necroses.
