Modeling of oxygen transport across tumor multicellular layers

Abstract

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 3-D model of tumor parenchyma, the multicellular layer (MCL).Methods-OCM-1 human choroidal melanoma cells were grown as 3-D MCL 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/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 permit the study of parameters important in tumor oxygenation in vitro.

Bioengineered three‐dimensional co‐culture of cancer cells and endothelial cells: A model system for dual analysis of tumor growth and angiogenesis

“…A more realistic HCC microenvironment consisting of a hypoxic core is generated within the 3D co‐culture (Braun and Beatty, ; Volkmer et al, ), and true gradient penetration of drugs is achieved (Gurski et al, ; Mehta et al, ) when compared to the 2D model. Due to the lack of oxygen and nutrients, vessel growth is initiated by the hypoxic core, where pro‐angiogenic factors and ECM proteins are secreted by cells, assisting in the establishment of a vascular network (Shen et al, ; Shirinifard et al, ).…”

3D culture broadly regulates tumor cell hypoxia response and angiogenesis via pro-inflammatory pathways

“…Given that growth in conventional 3D culture systems inevitably leads to heterogeneous oxygen distributions and resulting cellular phenotypes, it is challenging to distinguish these parameters [13, 14]. Because gene expression changes are typically determined as population averages, most 3D models preclude the association of culture context-dependent expression profiles to a specific oxygen level.…”

Oxygen profiles in egg masses predicted from a diffusion–reaction model

“…Given information about mass size, embryo O 2 consumption rates, number of embryos per unit volume of egg mass ('embryo density'), and diffusion coefficients, the model predicts O 2 concentrations anywhere in the structure and at any future time after a change in external O 2 concentrations. The model may be broadly applicable to other biological situations, as the basic set of mechanisms (oxygen diffusion and consumption) is responsible for establishing oxygen profiles in other structures, including tumors (Braun and Beatty, 2007), engineered tissues (Brown et al, 2007), insect eggs (Woods et al, 2005), and vertebrate embryos early in development (Kranenbarg et al, 2000).…”