Further Evidence that Gradients of Extracellular pH Direct Migration of MDA-MB-231 Cells In Vitro.

ABSTRACT

We hypothesised that concentration gradients of O2/H+ within tissue guide migration of primary cancer cells toward intra-tumour microvessels, thus promoting intravasation and eventual haematogenous metastasis of cancer cells. Previously, we demonstrated in vitro that MDA-MB-231 cells under pH and O2 gradients (0.2-0.3 units/mm and ~ 6%/mm, respectively) migrate toward higher pH/O2 regions. The present study was designed to address questions yet unanswered in the previous one, i.e., (1) whether extracellular O2 gradients could be a cue for directional cell migration in physiologically relevant O2 environments, and (2) whether average pH level in the bulk extracellular medium affects directional cell migration. In the absence of pH gradients, directional cell migration was not demonstrated at a physiological O2 level (<5%). We demonstrated that both the migration velocity and directionality are significantly affected by the average extracellular pH level. This result is consistent with our model for directional cell migration that does not necessitate sensing of pH gradient at a single cell level. Thus, in this study, we demonstrated further evidence that gradients of extracellular pH direct migration of MDA-MB-231 cells in vitro.