Abstract

The carbonic anhydrases (CAs) catalyse the hydration of CO₂ to bicarbonate at physiological pH. This chemical interconversion is crucial since HCO₃^- is the substrate for several biosynthetic reactions. Carbonic anhydrases are involved in many physiological processes connected with respiration and transport of CO₂/bicarbonate between metabolising tissues and the lungs, pH homeostasis and electrolyte secretion in a variety of tissues/organs. The present work was undertaken to study the distribution and expression of CA isoenzymes in the normal and neoplastic gastrointestinal tissues.

The expression of CA I, II, IX and XII in the human intestine and colorectal tumours was investigated by immunohistochemistry and western blotting. In the present study, immunohistochemical methods were also used to examine the location of CA IX and XII in the human pancreas and pancreatic tumours. The expression of CA XIV in the murine liver and intestine was studied using immunostaining and northern blotting.

The present results suggest that transmembrane CA XII is absent from the small intestine, but is expressed in all segments of the normal large intestine. The positive signal for CA XII was confined to the basolateral plasma membranes of the epithelial cells of the surface epithelial cuff. In tumours, the signal for CA XII became stronger in the deep part of the lesion. The intensity of the immunostaining for CA I and II was clearly found to decrease in benign lesions and became very weak in malignant colorectal tumours. The reciprocal pattern of expression observed for membrane-associated (CA IX and XII) and cytoplasmic (CA I and II) isoenzymes in intestinal samples suggests that CA IX and XII may be functionally involved in tumour progression to malignancy and/or in invasion. CA I and II, which are thought to play important physiological roles in the normal colorectal mucosa, may not be required for growth of colorectal cancers and their expression consistently diminishes with progression to malignancy.

In the human pancreas CA IX and XII appeared to be sporadically expressed in the basolateral plasma membrane of the normal acinar and ductal epithelium. The increased expression of CA IX in hyperplastic ductal epithelium may contribute to the pancreatic tumourigenesis.

CA XIV was expressed in the hepatocyte plasma membrane and its localization on both apical and basolateral membrane domains suggests an important role for this isoenzyme in the regulation of ion and pH homeostasis in the liver.