Carbonic anhydrase II in the endothelium of glial tumors: A potential target for therapy

Abstract

Carbonic anhydrase isozyme II (CA II) is a cytosolic enzyme that is highly expressed in most organs, including the brain, where it is mainly located in the oligodendrocytes. Recent studies have shown that its expression is induced in the endothelium of neovessels in melanoma and esophageal, renal, and lung cancer. Immunological studies further indicate that CA II represents a major target antigen stimulating an autoantibody response in melanoma patients. These results prompted us to investigate endothelial CA II expression in two types of brain cancer: oligodendrogliomas and astrocytomas. A series of 255 astrocytoma and 71 oligodendroglial tumor specimens was immunostained for CA II. The staining results were correlated with a number of different clinicopathological factors and survival data. CA II showed weak or no expression in low-grade tumors, while grade 3 mixed oligoastrocytoma and glioblastoma multiforme were the most positively stained tumor types. Survival analysis indicated that endothelial CA II staining is significantly associated with a poor prognosis in patients with astrocytomas. About 17% of patients with CA II-negative tumors (weak or no endothelial signal) were still alive at the end of the follow-up period of five years. The presence of CA II in the tumor endothelium suggests that it may play an important functional role in tumor metabolism. From a clinical perspective, the results also open new avenues for selecting tumor types for dendritic cell therapy trials.

Carbonic anhydrase VII–a potential prognostic marker in gliomas

“…This result makes CA VII another CA isozyme with a significant correlation to the patient survival. Indeed, the previous studies have demonstrated that CA II, CA IX and CA XII all show similar trends as prognostic markers in diffuse astrocytomas [6,7,25,39]. The presence of several CA isozymes in astrocytomas may reflect the rapid turnover of acid metabolic products in highly malignant tumor tissues.…”

“…Previous studies have indicated that carbonic anhydrase isozymes, CA II, CA IX and CA XII, are promising biomarkers for certain tumors [6,7,22,26]. There are numerous reports showing that CA IX acts not only as a marker for particular tumors, but its presence also correlates to prognosis in several tumor categories, such as brain tumors, sarcomas, and renal, lung, rectal, bladder, oral, breast, and cervical carcinomas [7,[27][28][29][30][31][32][33][34].…”

“…There are numerous reports showing that CA IX acts not only as a marker for particular tumors, but its presence also correlates to prognosis in several tumor categories, such as brain tumors, sarcomas, and renal, lung, rectal, bladder, oral, breast, and cervical carcinomas [7,[27][28][29][30][31][32][33][34]. Although studies on CA II and CA XII have been mainly focused on normal tissues, there are a few previous reports, showing their presence in cancer cells and especially in brain tumors where they have shown significant association with prognosis [6,7,25]. CA VII is a cytosolic isozyme which was first demonstrated in the brain tissue [35], where it has been linked to the regulation of GABAergic neuronal transmission in hippocampal neurons [36].…”

“…The α-CA gene family has been reported to include at least 13 active isoforms with different structural and catalytic properties [1][2][3][4][5]. CA isozymes II, IX and XII have been extensively studied for their important role as promising biomarkers in different tumors, for example astrocytic tumors [5][6][7]. Other important research targets focused on CAs have included hypoxia-regulation of certain CA isozymes and their potential use as targets of cancer therapy [7][8][9][10][11][12][13].…”

Reduction of CAII expression in gastric cancer: Correlation with invasion and metastasis

“…Human CAII gene, which locates at chromosome 8q22, codes a cytoplasmic protein that has the highest turnover rate and widest tissue distribution among the known human CA isozymes [3] . CAII is correlated with several types of tumors [9][10][11][12] . In our previous study, the expression of CAII was down-regulated in GC [2] .…”