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  • Blog
  • Story of CA IX (11443-1-AP)

Story of CA IX (11443-1-AP)

What are CAs?

The carbonic anhydrases (CAs; EC 4.2.1.1) are a family of metalloenzymes that catalyze the reversible hydration of carbon dioxide and bicarbonate. Among those identified, there are eight cytosolic proteins (CA I, CA II, CA III, CA VII, CA VIII, CA X, CA XI, CA XIII), two mitochondrial matrix proteins (CA VA, CA VB), one secreted protein (CA VI), two glycosylphosphatidylinositol (GPI)-anchored proteins (CA IV and CA XV), and three transmembrane proteins (CA IX, CA XII, CA XIV).

What is CA IX?

Carbonic anhydrase IX (CA IX) is the gene most widely expressed in response to hypoxia. Its crucial role in intracellular pH maintenance represents the means by which cancer cells adapt to the toxic conditions of the extracellular milieu. CA IX expression in many types of tumor indicates its relevance as a general marker of tumor hypoxia. Moreover, its expression is closely related to prognosis of the clinical outcome in several tumor types. All of the above-mentioned facts support the strong position of CA IX as a potential drug therapy target.

Why is CA IX important?

The CA IX protein is mainly involved in the following three aspects:

1. CA IX AS A DIAGNOSTIC MARKER

In 1986, using monoclonal antibody G250, a novel marker specific for renal cell carcinoma (RCC) was discovered. Among different RCC subtypes, clear cell renal cell carcinoma (CCRCC) is associated with the highest CA IX expression. The protein is expressed in 97% of CCRCC cases with apparently no expression in normal renal tissue. Therefore, CA IX bears the potential of being a diagnostic marker for renal malignancies. However, its expression is not only connected with numerous RCC subtypes, but with a whole spectrum of solid tumors. Large-scale studies of tumor-derived cell line and tissue specimens revealed CA IX expression in specific carcinomas of the cervix uteri and uterine corpus, ovary, gastrointestinal tract, liver, pancreas, lung, head/neck, salivary gland, body cavity, and skin. CA IX is thus a general marker of tumor hypoxia in many solid tumors rather than a specific marker for distinct types/subtypes of malignancies (1).