Upregulated Na+/H+-Exchange Protects Human Colon Cancer Tissue against Intracellular Acidification
Resting steady-state p and the capacity for net acid extrusion are elevated in human colon cancer tissue compared to normal colon tissue due to enhanced Na+/H+-exchange activity. (a) Images of BCECF-loaded colon crypts (495 nm excitation) isolated from normal colon tissue (left panel) and colon cancer tissue (right panel). The size bar represents 100 μm; both images are shown at the same magnification. (b) Steady-state p—measured at extracellular pH 7.4—is elevated in colon cancer tissue compared with normal colon tissue (n=8-9) both with and without CO2/HC present. We compared data by repeated-measures two-way ANOVA followed by Sidak’s posttests. (c) Original traces of p during N-prepulse experiments performed in the absence of CO2/HC. In the illustrated experiment performed in presence of 10 μM cariporide, this Na+/H+-exchange inhibitor was added at the time of NH4Cl washout and maintained in the bath solution for the rest of the experiment. (d) Intrinsic buffering capacity is similar in crypts from human colon cancer tissue and normal colon tissue (n=9-11). Based on least-squares linear regression analysis, we compared buffering capacities—plotted on a log-scale—as function of the corresponding p values calculated as the mean of the p before and after NH4Cl washout. Neither slope (P=0.80) nor intercept (P=0.10) differed significantly between the groups. (e+f) Rates of net acid extrusion plotted as function of p in crypts from human colon cancer tissue and normal colon tissue (n=8-11) in the presence (e) and absence (f) of CO2/HC. In the experiments (n=3) performed in presence of 10 μM cariporide, this Na+/H+-exchange inhibitor was added at the time of NH4Cl washout and maintained in the bath solution for the rest of the experiment. We compared lines by least-squares regression analyses and the effect of cariporide in normal and cancer tissue by two-way ANOVA. ,, and . NS: not significantly different vs. normal tissue under similar conditions. #P<0.05 vs. tissue without cariporide evaluated at similar p.
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