Vaupel P
Department of Radiotherapy and Radiooncology, Klinikum rechts der Isar, Munich Technical University, Ismaninger Strasse 22, Munich 81675, Germany.
Exp Oncol. 2010 Sep;32(3):125-7.
The hostile metabolic microenvironment of solid tumors, which is quite heterogeneous both spatially and temporally (« 4-D-heterogeneity »), can trigger malignant progression. Above all, acute and fluctuating hypoxia elicits multiple cellular response pathways that alter gene expression and phenotype (at moderate hypoxia with oxygen concentrations below 1%). Upon severe hypoxia (oxygen concentrations below 0.1%), genomic instability can lead to cell variants with adaptations favorable to survival. These cell variants have growth advantages in the hostile tumor microenvironment and finally expand through clonal selection thus promoting tumor aggressiveness. In addition to hypoxia, high lactate concentrations (above approximately 8 mM) may promote malignant progression. The interpretation of the role of tumor pH in tumor progression is complicated by the frequently occurring coexistence of tumor hypoxia and acidosis.
实体瘤的恶性代谢微环境在空间和时间上都具有很大的异质性（“4-D异质性”），可引发恶性进展。最重要的是，急性和波动的缺氧会引发多种细胞反应途径，从而改变基因表达和表型（在氧气浓度低于1%的中度缺氧情况下）。在严重缺氧（氧气浓度低于0.1%）时，基因组不稳定可导致具有有利于生存的适应性的细胞变体。这些细胞变体在恶劣的肿瘤微环境中具有生长优势，最终通过克隆选择而扩增，从而促进肿瘤侵袭性。除了缺氧外，高乳酸浓度（高于约8 mM）可能促进恶性进展。肿瘤缺氧和酸中毒的频繁共存使对肿瘤pH值在肿瘤进展中作用的解释变得复杂。
