Lactate dehydrogenase isoenzymes 1 and 5: differential expression by neoplastic and stromal cells in non-small cell lung cancer and other epithelial malignant tumors.
OBJECTIVE
Lactate dehydrogenase-5 (LDH-5), an isoenzyme composed of 4 M-polypeptide chains, catalyzes the conversion of pyruvate to lactate with an unparalleled efficiency (anaerobic oxidation), but this function of LDH gradually fades away as the number of H over M chains increases. Thus, LDH-1, another component isoenzyme made up of 4 H-polypeptide chains, favors aerobic oxidation of pyruvate by pyruvate dehydrogenase.


METHODS
Using immunohistochemistry in this study, we explored the expression of LDH-1 and LDH-5 in a variety of normal and malignant tissues, including lung, breast, endometrium, urinary bladder and large intestine.


RESULTS
LDH-1 was consistently expressed in all living cells, normal and malignant, epithelial and stromal, including endothelium and lymphocytes. In contrast, LDH-5 was expressed preferentially in tumor cells, while normal tissues were devoid of LDH-5 or expressed it only faintly, and the cellular population of the tumor-supporting stroma showed LDH-5 activity in a small percentage of cases. Interestingly, LDH-5-positive stromal cells were associated with hypoxia-inducible factor-1alpha overexpression.


CONCLUSIONS
It is concluded that normal tissues utilize aerobic oxidation as a means of energy production, while tumor cells are turned to anaerobic glycolysis, a phenomenon which is rarely followed by the mesenchymal cells of the tumor-supporting stroma.
Koukourakis
Michael I
MI
Department of Radiotherapy/Oncology, Democritus University of Thrace, Alexandroupolis, Greece.
Giatromanolaki
Alexandra
A
Sivridis
Efthimios
E
D001943:Breast Neoplasms / Q000201:enzymology; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000032:analysis*; D007770:L-Lactate Dehydrogenase / Q000032:analysis*; D000080864:Lactate Dehydrogenase 5; D008175:Lung Neoplasms / Q000201:enzymology*; D009375:Neoplasms, Glandular and Epithelial / Q000201:enzymology*; D017154:Stromal Cells / Q000201:enzymology*
D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5; C409667:lactate dehydrogenase 1