Tumor-Associated Carbonic Anhydrases IX and XII

Progression in tumorigenesis is often stimulated by microenvironmental factors such as hypoxia and acidosis leading to selection of cells with the most aggressive phenotype. Invasive cancer cell behavior is reinforced by extensive molecular modifications executed by hypoxia-inducible factor (HIF) via activation of a wide gene scale involved in adaptation to adverse milieu. HIF-upregulated molecules include transmembrane pH regulators carbonic anhydrase (CA) IX and XII that support tumor survival and therefore represent useful anticancer therapy targets. CA IX serves as a marker of hypoxia and prognostic indicator since its expression is closely related to different types of carcinomas and is strongly induced during hypoxia. Despite the fact that CA XII shows less tight association with cancer, it bears prognostic potential due to its link to well-differentiated tumors. In this chapter, we summarize current knowledge on these two cancer-associated CAs and provide insight into their role in tumor cell biology.