Tumor-associated carbonic anhydrase XII is linked to the growth of primary oral squamous cell carcinoma and its poor prognosis

Chien, Ming Hsien; Ying, Tsung Ho; Hsieh, Yi‐Hsien; Lin, Chien Huang; Shih, Chun Han; Wei, Lin-Hung; Yang, Shun Fa

doi:10.1016/j.oraloncology.2011.11.015

Cited by 50 publications

(33 citation statements)

References 42 publications

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“…CA12 is associated with poor prognosis 101 also responsible for tumor invasion 102 and associated with poor prognosis 103 while other data suggested CA12 is related to good prognosis 104,105 . These data collectively reveal that CA12 overexpressed preferentially at the edge of the tumor (distally from necrotic regions).…”

Section: Carbonic Anhydrase 12 (Caxi)mentioning

confidence: 96%

Tumor metabolism, cancer cell transporters, and microenvironmental resistance

Alfarouk

2016

Journal of Enzyme Inhibition and Medicinal Chemistry

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Cancer cells reprogram their metabolic machineries to enter into permanent glycolytic pathways. The full reason for such reprogramming takes place is unclear. However, this metabolic switch is not made in vain for the lactate that is generated and exported outside cells is reused by other cells. This results in the generation of a pH gradient between the low extracellular pH that is acidic (pHe) and the higher cytosolic alkaline or near neutral pH (pHi) environments that are tightly regulated by the overexpression of several pumps and ion channels (e.g. NHE-1, MCT-1, V-ATPase, CA9, and CA12). The generation of this unique pH gradient serves as a determining factor in defining ''tumor fitness''. Tumor fitness is the capacity of the tumor to invade and metastasize due to its ability to reduce the efficiency of the immune system and confer resistance to chemotherapy. In this article, we highlight the importance of tumor microenvironment in mediating the failure of chemotherapeutic agents.

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Section: Carbonic Anhydrase 12 (Caxi)mentioning

confidence: 96%

Tumor metabolism, cancer cell transporters, and microenvironmental resistance

Alfarouk

2016

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…In contrast to CA IX, CA XII is upregulated by estrogen and therefore present in many breast cancers (3). More generally, the enzyme is overexpressed in many forms of human cancer, including renal, pancreatic, gut, oral, brain, lung, and ovarian (2,(4)(5)(6)(7)(8)(9)(10)(11), but is also present in some normal tissues, such as kidney, gut, and endometrium (4,6,12), expressed in combination with other carbonic anhydrase isoforms. CA XII has also been found to be overexpressed in glaucoma (13) and in advanced atherosclerotic plaques (14).…”

Section: Introductionmentioning

confidence: 99%

Antitumor Efficacy of a Monoclonal Antibody That Inhibits the Activity of Cancer-Associated Carbonic Anhydrase XII

et al. 2013

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Carbonic anhydrase XII (CA XII) is a membrane-tethered cell surface enzyme that is highly expressed on many human tumor cells. Carbonic anhydrase members in this class of exofacial molecules facilitate tumor metabolism by facilitating CO 2 venting and intracellular pH regulation. Accordingly, inhibition of exofacial CAs has been proposed as a general therapeutic strategy to target cancer. The recent characterization of 6A10, the first CA XII-specific inhibitory monoclonal antibody, offered an opportunity to evaluate this strategy with regard to CA XII-mediated catalysis. Using functional assays, we showed that 6A10 inhibited exofacial CA activity in CA XIIexpressing cancer cells. 6A10 reduced spheroid growth in vitro under culture conditions where CA XII was active (i.e., alkaline pH) and where its catalytic activity was likely rate-limiting (i.e., restricted extracellular HCO 3 À supply). These in vitro results argued that the antibody exerted its growth-retarding effect by acting on the catalytic process, rather than on antigen binding per se. Notably, when administered in a mouse xenograft model of human cancer, 6A10 exerted a significant delay on tumor outgrowth. These results corroborate the notion that exofacial CA is critical for cancer cell physiology and they establish the immunotherapeutic efficacy of targeting CA XII using an inhibitory antibody. Cancer Res; 73(21); 6494-503. Ó2013 AACR.

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“…The enhanced activity of CAs is often related to various diseases. The isoforms CA IX and CA XII were intensively investigated enzymes during the last decade due to their overexpression in various human cancers [5][6][7][8][9] . Much work has been done to design selective CA IX and CA XII inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Benzenesulfonamides with benzimidazole moieties as inhibitors of carbonic anhydrases I, II, VII, XII and XIII

Zubrienė

Čapkauskaitė

Gylytė

et al. 2013

Journal of Enzyme Inhibition and Medicinal Chemistry

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A series of benzenesulfonamide derivatives, bearing benzimidazole moieties, were designed and synthesized as inhibitors of carbonic anhydrases (CAs). Their binding affinities to recombinant human CA isozymes I, II, VII, XII and XIII were determined by the thermal shift assay. A group of compounds containing a benzimidazole substituent in the para position of the benzenesulfonamide ring was found to exhibit higher binding potency toward tested CAs than meta-substituted benzenesulfonamides. Some of these compounds exhibited nanomolar affinities and selectivity toward the CA isozymes tested.

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Tumor-associated carbonic anhydrase XII is linked to the growth of primary oral squamous cell carcinoma and its poor prognosis

Cited by 50 publications

References 42 publications

Tumor metabolism, cancer cell transporters, and microenvironmental resistance

Tumor metabolism, cancer cell transporters, and microenvironmental resistance

Antitumor Efficacy of a Monoclonal Antibody That Inhibits the Activity of Cancer-Associated Carbonic Anhydrase XII

Benzenesulfonamides with benzimidazole moieties as inhibitors of carbonic anhydrases I, II, VII, XII and XIII

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