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Lactate dehydrogenase 5 (LDH5) relates to up-regulated hypoxia inducible factor pathway and metastasis in colorectal cancer

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Abstract

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) 1α and 2α. 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 HIF1α and HIF2α, 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 HIF1α and HIF2α accumulation. HIF1α 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 lnked with an aggressive phenotype in colorectal adenocarcinomas.

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Abbreviations

ATP:

adenosine triphosphate

DAB:

diaminobenzidine

HIF:

hypoxia inducible factor

LDH5:

lactate dehydrogenase

NAD+ :

nicotinamide adenine dinucleotide

NADH:

dihydronicotinamide adenine dinucleotide

TBS:

Tris-buffered saline

VD:

vascular density

VEGF:

vascular endothelial growth factor

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Authors and Affiliations

  1. Department of Radiotherapy/Oncology, Democritus University of Thrace Medical School, 68100, Alexandroupolis, Greece

    Michael I. Koukourakis

  2. Department of Pathology, Democritus University of Thrace Medical School, Alexandroupolis, Greece

    Alexandra Giatromanolaki & Efthimios Sivridis

  3. Second University Department of Surgery, Democritus University of Thrace, Alexandroupolis, Greece

    Costantinos Simopoulos & Alexandros Polychronidis

Authors
  1. Michael I. Koukourakis
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  2. Alexandra Giatromanolaki
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  3. Costantinos Simopoulos
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  4. Alexandros Polychronidis
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  5. Efthimios Sivridis
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Correspondence to Michael I. Koukourakis.

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Koukourakis, M.I., Giatromanolaki, A., Simopoulos, C. et al. Lactate dehydrogenase 5 (LDH5) relates to up-regulated hypoxia inducible factor pathway and metastasis in colorectal cancer. Clin Exp Metastasis 22, 25–30 (2005). https://doi.org/10.1007/s10585-005-2343-7

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  • DOI: https://doi.org/10.1007/s10585-005-2343-7

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