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Renal Cell Carcinoma pp 253–270Cite as

Carbonic Anhydrase IX: Its Role as a Biomarker, Diagnostic, and Therapeutic Target in Renal Cell Carcinoma

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Abstract

The distribution of CAIX was first described in 1986 (then named G250-antigen) in an immunohistochemical study describing the specificity analysis and tumor specificity of mAb G250. Based on this analysis, it was suggested that the recognized moiety could potentially serve as a target for therapy and/or diagnosis in RCC [1]. Subsequent studies demonstrated that the antigen recognized, carbonic anhydrase IX (CAIX) [2], is a transmembrane glycoprotein belonging to the carbonic anhydrase group of enzymes. These ubiquitous metalloenzymes act as catalysts in the reversible hydration of CO2 to HCO −3 and H+ and are critical in the regulation of proton flux in cells and thus in pH regulation [3]. In contrast to most carbonic anhydrases, the catalytic site of CAIX is located extracellularly, where it is involved in pH regulation [4]: the extracellularly located CAIX catalytic domain converts CO2 produced in the cytoplasm of cells and diffused through the plasma membrane into bicarbonate and protons contributing to extracellular acidosis. The newly generated HCO −3 ions can then be transported back into the tumor cells or to blood capillaries by HCO −3 transport proteins. This coupled transport process is probably essential for cancer cells to buffer their intracellular pH value to near neutral conditions necessary for survival [5]. Recent biochemical and crystallographic data showed that CAIX was present as a dimeric protein, with the dimerization mediated by the formation of an intermolecular disulfide bond between the same Cys residue located on two CA catalytic domains [6, 7].

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Authors and Affiliations

  1. Department of Urology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

    E. Oosterwijk Ph.D., A. B. Stillebroer M.D. & P. F. A. Mulders M.D., Ph.D.

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  1. E. Oosterwijk Ph.D.
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  1. David Geffen School of Medicine at UCLA, Department of Medicine, Cedars-Sinai Medical Center, n/a, Los Angeles, 90095, California, USA

    Robert A. Figlin

  2. Lineberger Comprehensive Cancer Center, University of North Carolina, Campus Box 7295, Room 21-237, 218, Chapel Hill, 27599-7295, North Carolina, USA

    W. Kimryn Rathmell

  3. Taussig Cancer Institute, Department of Solid Tumor Oncology, Cleveland Clinic, 9500 Euclid Ave, CLEVELAND, 44195-0001, Ohio, USA

    Brian I. Rini

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Oosterwijk, E., Stillebroer, A.B., Mulders, P.F.A. (2012). Carbonic Anhydrase IX: Its Role as a Biomarker, Diagnostic, and Therapeutic Target in Renal Cell Carcinoma. In: Figlin, R., Rathmell, W., Rini, B. (eds) Renal Cell Carcinoma. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-2400-0_12

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