The Intrinsic Mitochondrial Membrane Potential of Colonic Carcinoma Cells Is Linked to the Probability of Tumor Progression

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Abstract
We subcloned cell lines from SW620 cells establishing that, despite the dynamic nature of the mitochondrial membrane potential (Δψm), there are significant and stable differences in the intrinsic Δψm among cells within an in vitro population of human colonic carcinoma cells. Whereas more dramatic differences in Δψm would likely perturb essential mitochondrial functions, the differences in Δψm of the subclones did not affect steady-state reactive oxygen species levels, electron transport activity, or cellular viability and growth rates. However, the differences in intrinsic Δψm had a significant effect on the tumorigenic behavior of the cells. Subcloned cell lines with higher Δψm were more likely to exhibit elevated steady-state levels of vascular endothelial growth factor and matrix metalloproteinase 7, and increased invasive behavior (properties associated with tumor progression), than cells with lower intrinsic Δψm, whereas cells with lower Δψm were more likely to respond to the chemopreventive activities of butyrate, including Δψm dissipation, growth arrest, and apoptosis, than cells with higher Δψm. Therefore, these data establish that the probability for tumor development and progression is linked to stable differences in the intrinsic Δψm of colonic epithelial cells.