Mathematical Modelling of Tumor Acidity: Regulation of Intracellular pH

The carbonic anhydrase I locus contains a c-Myb target promoter and modulates differentiation of murine erythroleukemia cells

“…Thus, the altered rates of differentiation that we observe in our CAI stable transfectants relative to C19 MEL cells may be due in part to changes in extracellular pH due to the different amounts of CAI protein expression. In support of this notion, it is of interest to consider reports that extracellular pH in solid tumors is more acidic than in adjacent normal tissue, and that acidification of the extracellular environment of malignant tumors may increase the invasive behavior of cancer cells (Webb et al, 1999;Cardone et al, 2005). For example, it has been reported that human melanoma cells cultured in acidic growth medium have a greater invasive potential than when tested in medium at standard pH (Martinez-Zaguilan et al, 1996).…”

Necrotic core in EMT6/Ro tumour spheroids: Is it caused by an ATP deficit?

“…These effects seem to depend on the pH of cell environment: for instance, the Crabtree effect disappears in an acidic environment. Although the production of H + ions is related to lactic acid production, the description of pH changes is complicated by the presence of an intracellular buffer (see the mathematical models in Casciari et al, 1992, andWebb et al, 1999). Since a mechanistic representation of these phenomena appears to be rather complex, they are neglected in our model.…”

A stochastic multiscale model for acid mediated cancer invasion

“…1 To acquire a concrete form for these transporter terms -in the absence of numerical data -we followed e.g., [46] and tried to mimic for T 1 and T 2 functions the qualitative curves obtained experimentally in [4] for the efflux of protons by NDCBE and NHE in MGU-1 cell lines. For the T 3 function we adopted the approach in [46] and made it a monotone decreasing function of H i , since the AE acts as a counter-mechanism for the alkalinization of cytoplasm. Furthermore, Q denotes the function representing the loss of free protons due to intracellular buffering (e.g., by organelles).…”

“…It is clear, however, that subcellular, microlevel proton dynamics are actually regulating and are influenced significantly by the events on the higher (i.e., macroscopic and mesoscopic) levels [27,38,44]. Mathematical models studying the interdependence between the activity of several membrane ion transport systems and the changes in the peritumoral space were proposed by Webb et al [46,45]. They also involve intracellular proton buffering, effects on the expression/activation of MMPs and proton removal by vasculature.…”