Oxygen and glucose consumption in gastrointestinal adenocarcinomas: correlation with markers of hypoxia, acidity and anaerobic glycolysis.
This study gives an insight into tumor metabolic activity by investigating oxygen and glucose content, together with their metabolic products carbon dioxide and acids-pH, in the arterial and venous blood of a tumor. Nineteen patients with gastrointestinal adenocarcinomas undergoing surgery were studied. Biochemical analysis showed that in a large subgroup of tumors, oxygen consumption was reduced while that of glucose was increased in malignant, as compared to normal tissues; these features were more evident in tumors overexpressing lactate dehydrogenase (LDH-5) and hypoxia inducible factors (HIF1alpha/2alpha). An increase in carbon dioxide production in the tumor environment was linked with overexpression of carbonic anhydrase 9 (CA9). The simultaneous overexpression of CA9 and LDH-5 was related to very low pH levels in the veins draining the tumor, suggesting an intense acidification of the tumor microenvironment in such cases. These in vivo data confirm the importance of HIFs and their downstream regulated genes in tumor metabolism, particularly in glycolysis and carbon dioxide buffering.
Koukourakis
Michael I
MI
Department of Radiotherapy/Oncology, Democritus University of Thrace Medical School, Dragana, Alexandroupolis, Greece. targ@her.forthnet.gr
Pitiakoudis
Michael
M
Giatromanolaki
Alexandra
A
Tsarouha
Alexandra
A
Polychronidis
Alexandros
A
Sivridis
Efthimios
E
Simopoulos
Costantinos
C
D000138:Acidosis / Q000378:metabolism; D000230:Adenocarcinoma / Q000378:metabolism*; D000693:Anaerobiosis; D000951:Antigens, Neoplasm / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers / Q000097:blood; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D001786:Blood Glucose / Q000032:analysis; D002245:Carbon Dioxide / Q000097:blood; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000378:metabolism*; D006019:Glycolysis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D007527:Isoenzymes / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D000080864:Lactate Dehydrogenase 5; D008297:Male; D010101:Oxygen Consumption; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D000099162:Endothelial PAS Domain-Containing Protein 1
D000951:Antigens, Neoplasm; D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D014408:Biomarkers, Tumor; D001786:Blood Glucose; D002245:Carbon Dioxide; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5; D014157:Transcription Factors; D000099162:Endothelial PAS Domain-Containing Protein 1; C089226:CA9 protein, human