Mechanisms of buffer therapy resistance

摘要: Many studies have shown that the acidity of solid tumors contributes to local invasion and metastasis. Oral pH buffers can specifically neutralize acidic reduce incidence metastatic formation in multiple murine models. However, this effect is not universal as we previously observed metastasis inhibited by some tumor models, regardless buffer used. B16-F10 (murine melanoma), LL/2 lung) HCT116 (human colon) are resistant treatment with lysine therapy, whereas potently MDA-MB-231 breast) PC3M prostate) tumors. In current work, confirmed sensitive cells utilized a pH-dependent mechanism for successful supported highly glycolytic phenotype acidifies microenvironment resulting morphological changes. contrast, buffer-resistant cell lines exhibited pH-independent involving constitutive secretion matrix degrading proteases without elevated glycolysis. These results identified two distinct mechanisms experimental metastasis, one which (buffer therapy cells) cells). Further characterization these models has potential therapeutic benefit.