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 (PO2) 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 PO2=0. Results: Depending upon the presence of a central region of anoxia, the PO2 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/mu m(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 pen-nit the study of parameters important in tumor oxygenation in vitro. (c) 2006 Elsevier Inc. All rights reserved.