Lactate dehydrogenase isoenzymes 1 and 5: differential expression by neoplastic and stromal cells in non-small cell lung cancer and other epithelial malignant tumors

Tumour Biol. Aug-Sep 2003;24(4):199-202. doi: 10.1159/000074430.

Abstract

Background/aims: 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / enzymology
  • Carcinoma, Non-Small-Cell Lung / enzymology*
  • Female
  • Humans
  • Immunohistochemistry
  • Isoenzymes / analysis*
  • L-Lactate Dehydrogenase / analysis*
  • Lactate Dehydrogenase 5
  • Lung Neoplasms / enzymology*
  • Neoplasms, Glandular and Epithelial / enzymology*
  • Stromal Cells / enzymology*

Substances

  • Isoenzymes
  • L-Lactate Dehydrogenase
  • Lactate Dehydrogenase 5
  • lactate dehydrogenase 1