Lung cancer: a comparative study of metabolism related protein expression in cancer cells and tumor associated stroma.
Immunohistochemical evaluation of lung carcinomas for key enzymes involved in cellular metabolism (lactate dehydrogenase LDH 1 and 5, pyruvate dehydrogenase PDH, pyruvate dehydrogenase kinase PDHK-1, monocarboxylate transporters MCT 1, 2 and 4, glucose transporter GLUT1, hypoxia inducible factors HIF1alpha and 2alpha) show a complementary metabolic profile between cancer cells and tumor-associated stroma. Cancer cells share enzyme/transporter activities suggestive of an anaerobic metabolism with high affinity for glucose absorption, anaerobic glycolysis and lactate extrusion. On the other hand, the tumour-associated fibroblasts express patterns involved in aerobic pathways and lactate oxidation. These findings bring forward the hypothesis that tumor associated stroma is an accomplice in tumor growth and survival sustaining an independent cellular and metabolic tumor domain. The development of agents exploiting such cancer specific metabolic pathways may prove of importance in the treatment of lung cancer.
Koukourakis
Michael I
MI
Department of Radiotherapy and Oncology, Democritus University of Thrace, Alexandroupolis, Greece. targ@her.forthnet.gr
Giatromanolaki
Alexandra
A
Bougioukas
Georgios
G
Sivridis
Efthimios
E
D000951:Antigens, Neoplasm / Q000378:metabolism; D045744:Cell Line, Tumor; D018450:Disease Progression; D005347:Fibroblasts / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005947:Glucose / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D007773:Lactates / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D008954:Models, Biological; D010100:Oxygen / Q000378:metabolism; D017154:Stromal Cells / Q000473:pathology
D000951:Antigens, Neoplasm; D051272:Glucose Transporter Type 1; D007773:Lactates; C495677:SLC2A1 protein, human; D005947:Glucose; D010100:Oxygen