Koukourakis Michael I, Giatromanolaki Alexandra, Simopoulos Costantinos, Polychronidis Alexandros, Sivridis Efthimios
Department of Radiotherapy/Oncology, Democritus University of Thrace Medical School, 68100 Alexandroupolis, Greece.
Clin Exp Metastasis. 2005;22(1):25-30. doi: 10.1007/s10585-005-2343-7.
Lactate dehydrogenase 5 (LDH5) is one of the five LDH isoenzymes and, apparently, the most important for promoting anaerobic glycolysis. LDH5 is transcriptionally regulated by the hypoxia inducible factors (HIF) 1alpha and 2alpha. In this study, the possible aggressive advantages that colorectal tumours may gain from a high LDH5 content was investigated. To this end, 75 colorectal adenocarcinomas were studied immunohistochemically for the expression of LDH5, and the results were related to tumor differentiation, lymph node and distant metastases, the expression of HIF1alpha and HIF2alpha, vascular density (VD) and vascular endothelial growth factor (VEGF). A high LDH5 content was noted in 51 of 75 (68%) colorectal adenocarcinomas. The reactivity was nuclear and/or cytoplasmic. Nuclear LDH5 reactivity was correlated with lymph node involvement and distant metastases. There was a direct association between LDH5 up-regulation and HIF1alpha and HIF2alpha accumulation. HIF1alpha was linked with VEGF, VD and also with extramural invasion, nodal and distant metastases. It is concluded that a high LDH5 content in tumor cells is directly related to an up-regulated HIF pathway and is linked with an aggressive phenotype in colorectal adenocarcinomas.
乳酸脱氢酶5（LDH5）是五种LDH同工酶之一，显然也是促进无氧糖酵解最重要的一种。LDH5受缺氧诱导因子（HIF）1α和2α的转录调控。在本研究中，调查了结直肠癌高LDH5含量可能带来的侵袭性优势。为此，对75例结直肠腺癌进行免疫组织化学研究，检测LDH5的表达，并将结果与肿瘤分化、淋巴结和远处转移、HIF1α和HIF2α的表达、血管密度（VD）以及血管内皮生长因子（VEGF）相关联。75例结直肠腺癌中有51例（68%）LDH5含量高。反应性为核反应和/或胞质反应。核LDH5反应性与淋巴结受累和远处转移相关。LDH5上调与HIF1α和HIF2α积累之间存在直接关联。HIF1α与VEGF、VD相关，也与壁外侵犯、淋巴结和远处转移相关。结论是肿瘤细胞中高LDH5含量与HIF途径上调直接相关，并与结直肠腺癌的侵袭性表型相关。
