Julius-Bernstein-Institute of Physiology, University of Halle-Wittenberg, Halle (Saale), Germany.
Adv Exp Med Biol. 2021;1269:151-155. doi: 10.1007/978-3-030-48238-1_24.
Tumor tissue shows special features in metabolism in contrast to healthy tissue. Besides a distinctive oxygen deficiency, tumors often show a reduced extracellular pH (acidosis) resulting from an intensified glycolysis not only under hypoxic but also under normoxic conditions (Warburg effect). As shown in previous studies, cell migration is increased in AT1 prostate carcinoma cells after incubation at pH 6.6, and this leads to an increased number of lung metastases in vivo. However, the signaling pathway causing these functional changes is still unknown. Possible mediators could be acidosis-regulated microRNAs (miR-7, miR-183, miR-203, miR-215). The aim of the study was therefore to analyze whether a change in the expression of these microRNAs has an impact on the tumor cell migration and adhesion. Studies were performed with AT1 rat prostate cancer cells which were incubated for 24 h at pH 7.4 or 6.6. Keeping AT1 tumor cells at low pH increased the migratory capacity by about 100%. But also the decrease of miR-203 and miR-215 expression (at normal pH) led to an increase in migration velocity by 50%. In contrast, cell adhesion was increased by about 75% at low pH. However, an increase in miR-215 expression at pH 6.6 reduced the adhesion by trend. These results clearly indicated that the extracellular pH has an impact on migration and adhesion of tumor cells. In this mechanism, pH-regulated microRNAs could play a role since changes in the expression of these microRNAs (especially miR-203) are also able to modulate the migratory behavior.
肿瘤组织的代谢与健康组织相比具有特殊特征。除了明显的缺氧外，肿瘤通常还表现出细胞外 pH 值降低（酸中毒），这是由于糖酵解增强所致，不仅在缺氧条件下，而且在常氧条件下也是如此（瓦博格效应）。如先前的研究所示，在 pH 6.6 下孵育后，AT1 前列腺癌细胞的细胞迁移增加，这导致体内肺转移的数量增加。然而，导致这些功能变化的信号通路仍不清楚。可能的调节剂可以是酸中毒调节的 microRNAs（miR-7、miR-183、miR-203、miR-215）。因此，本研究的目的是分析这些 microRNAs 的表达变化是否对肿瘤细胞迁移和黏附产生影响。研究使用 AT1 大鼠前列腺癌细胞进行，这些细胞在 pH 7.4 或 6.6 下孵育 24 小时。将 AT1 肿瘤细胞保持在低 pH 值可使迁移能力增加约 100%。但是，miR-203 和 miR-215 表达的降低（在正常 pH 值下）也导致迁移速度增加 50%。相比之下，低 pH 值可使细胞黏附增加约 75%。然而，pH 6.6 时 miR-215 表达的增加趋势降低了黏附。这些结果清楚地表明，细胞外 pH 值对肿瘤细胞的迁移和黏附有影响。在这种机制中，pH 调节的 microRNAs 可能发挥作用，因为这些 microRNAs（尤其是 miR-203）表达的变化也能够调节迁移行为。
