Differential effect of hypoxia and acidity on lung cancer cell and fibroblast metabolism.
This study examined the metabolic response of lung cancer cells and normal lung fibroblasts to hypoxia and acidity. GLUT1 and HXKII mRNA/protein expression was up-regulated under hypoxia in the MRC5 fibroblasts and in the A549 and H1299 lung cancer cell lines, indicating intensified glucose absorption and glycolysis. Under hypoxia, the LDHA mRNA and LDH5 protein levels increased in the cancer cells but not in the fibroblasts. Acidity suppressed the above-mentioned hypoxia effect. PDH-kinase-1 (PDK1 mRNA and protein) and inactive phosphorylated-PDH protein levels were induced under hypoxia in the cancer cells, whereas these were reduced in the MRC5 lung fibroblasts. In human tissue sections, the prevalent expression patterns supported the contrasting metabolic behavior of cancer cells vs. tumor fibroblasts. The monocarboxylate/lactate transporter 1 (MCT1) was up-regulated in all the cell lines under hypoxic conditions, but it was suppressed under acidic conditions. The mitochondrial DNA (mtDNA) content per cell decreased significantly in the A549 cancer cell line under hypoxia, but it increased in the MRC5 fibroblasts. Taking into account these findings, we suggest that, under hypoxia, cancer cells intensify the anaerobic direction in glycolysis, while normal fibroblasts prefer to seek energy by intensifying the aerobic use of the available oxygen.
a Department of Pathology, Democritus University of Thrace, and University General Hospital of Alexandroupolis, Alexandroupolis 68100, Greece.
Alexandra
A
Giatromanolaki
b Department of Radiotherapy/Oncology, Democritus University of Thrace, and University General Hospital of Alexandroupolis, Alexandroupolis 68100, Greece.
Maria
M
Liousia
a Department of Pathology, Democritus University of Thrace, and University General Hospital of Alexandroupolis, Alexandroupolis 68100, Greece.
Stella
S
Arelaki
b Department of Radiotherapy/Oncology, Democritus University of Thrace, and University General Hospital of Alexandroupolis, Alexandroupolis 68100, Greece.
Dimitra
D
Kalamida
b Department of Radiotherapy/Oncology, Democritus University of Thrace, and University General Hospital of Alexandroupolis, Alexandroupolis 68100, Greece.
Stamatia
S
Pouliliou
b Department of Radiotherapy/Oncology, Democritus University of Thrace, and University General Hospital of Alexandroupolis, Alexandroupolis 68100, Greece.
Achilleas
A
Mitrakas
b Department of Radiotherapy/Oncology, Democritus University of Thrace, and University General Hospital of Alexandroupolis, Alexandroupolis 68100, Greece.
Avgi
A
Tsolou
a Department of Pathology, Democritus University of Thrace, and University General Hospital of Alexandroupolis, Alexandroupolis 68100, Greece.
Efthimios
E
Sivridis
b Department of Radiotherapy/Oncology, Democritus University of Thrace, and University General Hospital of Alexandroupolis, Alexandroupolis 68100, Greece.
Michael
M
Koukourakis
D000143:Acids / Q000494:pharmacology*; D015153:Blotting, Western; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism*; D006593:Hexokinase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D027501:Monocarboxylic Acid Transporters / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D000099233:Monocarboxylate Transport Protein 1
D000143:Acids; D051272:Glucose Transporter Type 1; D006593:Hexokinase; D027501:Monocarboxylic Acid Transporters; D012333:RNA, Messenger; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1; C495677:SLC2A1 protein, human
ADNmt; acidity; acidité; cancer du poumon; fibroblaste pulmonaire; hypoxia; hypoxie; lung cancer; lung fibroblast; metabolism; mtDNA; métabolisme