Carbonic anhydrase IX in malignant pleural mesotheliomas: a potential target for anti-cancer therapy

Bioorg Med Chem. 2013 Mar 15;21(6):1483-8. doi: 10.1016/j.bmc.2012.09.018. Epub 2012 Sep 18.

Abstract

Malignant mesothelioma is a neoplasm deriving from mesothelial cells, which line the body cavities. The most common type is malignant pleural mesothelioma (MPM), which is a locally aggressive malignancy with poor prognosis. To improve both the clinical diagnostics and treatment it is necessary to identify novel molecular targets which are characteristic for MPM. Although carbonic anhydrase (CA) enzymes have been linked to pH regulation and spread of cancer cells, they have not been thoroughly studied in MPM specimens. We investigated by immunohistochemistry the expression of CA isozymes II, VII, IX, and XII in a series of 27 histological MPM tumor samples. CA IX was absent in the normal lung alveolar cells, whereas it was abundantly expressed in the normal pleural mesothelium and malignant mesothelioma cells. CA VII also showed weak or moderate reactions in several cases of mesotheliomas. Neither high expression of CA VII nor CA IX did correlate significantly with the survival of the patients. The very high expression of CA IX in MPM suggests that it could represent a novel molecular target for cancer research applications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / chemistry
  • Antigens, Neoplasm / metabolism*
  • Antineoplastic Agents / therapeutic use
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases / chemistry
  • Carbonic Anhydrases / metabolism*
  • Humans
  • Hydrogen-Ion Concentration
  • Immunohistochemistry
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / metabolism
  • Mesothelioma / drug therapy
  • Mesothelioma / enzymology*
  • Mesothelioma / pathology
  • Pleural Neoplasms / drug therapy
  • Pleural Neoplasms / enzymology*
  • Pleural Neoplasms / pathology
  • Survival Rate

Substances

  • Antigens, Neoplasm
  • Antineoplastic Agents
  • Isoenzymes
  • CA9 protein, human
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases