Alterations in proteolytic activity at low pH and its association with invasion: a theoretical model.

摘要: The extracellular pH (pHe) of solid tumours is often lower than in normal tissues, with median values about 7.0 and 7.5 tissue. Despite this more acidic tumour microenvironment, non-invasive measurements intracellular (pHi) have shown that the pHi neutral or slightly alkaline compared to tissue (pHi 7.0–7.4). This gives rise a reversed cellular gradient between tissue, which has been implicated many aspects progression. One such area invasion: incubation cells at low induce aggressive invasive behaviour vitro. In paper authors use mathematical models investigate whether altered proteolytic activity responsible for stimulation metastatic phenotype. examined effect culture on secretion two different classes proteinases: metalloproteinases (MMPs), cysteine proteinases (such as cathepsin B). modelling suggests changes MMP do not significant effects behaviour. However, model predicts levels active-cathepsin B are significantly by pH. result critical role