Modeling of oxygen transport across tumor multicellular layers.

PURPOSE: Tumor oxygen level plays a major role in the response of tumors to different treatments. The purpose of this study was to develop a method of determining oxygen transport properties in a recently developed 3D model of tumor parenchyma, the multicellular layer (MCL).
METHODS: OCM-1 human choroidal melanoma cells were grown as 3D MCLs on collagen-coated culture plate inserts. A recessed-cathode oxygen microelectrode was used to measure oxygen tension (PO(2)) profiles across 8 different MCL from the free surface to the insert membrane. The profiles were fitted to four different one-dimensional diffusion models: 1-, 2-, and 3-region models with uniform oxygen consumption (q) in each region and a modified 3-region model with a central region where q=0 and PO(2)=0.
RESULTS: Depending upon the presence of a central region of anoxia, the PO(2) profiles were fitted best by either the two-region model or the modified 3-region model. Consumption of tumor cells near the insert membrane was higher than that of cells close to the free surface (33.1+/-13.6 x 10(-4) vs. 11.8+/-6.7 x 10(-4) mm Hg/mum(2), respectively).
CONCLUSIONS: The model is useful for determining oxygenation and consumption in MCL, especially for cell lines that cannot be grown as spheroids. In the future, this model will permit the study of parameters important in tumor oxygenation in vitro.