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Posts Tagged ‘Carbonic Anhydrase IX’

Marking Hypoxia and Cancer with CAIX

Thursday, October 24th, 2013

Carbonic anhydrase IX (CAIX) is a member of the carbonic anhydrase family – enzymes that enable the rapid conversion of carbon dioxide and water into carbonic acid, protons, and bicarbonate ions. Carbonic anhydrases have a widespread role in regulating pH in normal tissues and are abundantly found in all mammalian tissues. CAIX itself is one of the most hypoxically-inducible genes due to its stability and membrane location. It has become a reliable hypoxia histochemical marker, as well as an important diagnostic marker for various cancers, most notably renal cell carcinoma (RCC). A Swiss group used the CAIX antibody in their differential PET imaging studies with tracers in preclinical mouse models (1). These investigators were establishing and monitoring three different osteosarcoma phenotypes for metabolic activity, hypoxia, and bone remodeling, and histology and immunohistochemistry (IHC) with the CAIX antibody enabled them to confirm their PET findings.

Immunohistochemistry: Carbonic Anhydrase IX Antibody

Immunohistochemistry: Carbonic Anhydrase IX Antibody

Pistollato, et. al. used the CAIX antibody to map networks and make strong correlations between intratumoral conditions, tumor phenotype, and tumor resistance to chemotherapy in highly proliferative glioblastoma multiforme (GBM) tumors (2).  A multivariate analysis of prognostic factors in patients with advanced RCC relied upon a panel of profiling antibodies, including the CAIX antibody, to demonstrate the strength of markers such as HIF-1 alpha, PTEN, p21, thrombocytosis, neutrophilia, and CAIX over others that were not as promising (3). Some recent and interesting studies from the Netherlands using the CAIX antibody suggest that newly designed dual-targeting anti-CAIX drugs combine both strong anti-tumor efficacies with beneficially low off-target effects (4).

  1. PMID: 23801674
  2. PMID: 22959659
  3. PMID: 22959659
  4. PMID: 23849171

Novus Biologicals offers CAIX reagents for your research needs including:

Carbonic Anhydrase IX Roles in Tumor Growth, Survival and Invasion

Friday, September 7th, 2012

Carbonic anhydrase IX (CAIX) is a membrane-associated carbonic anhydrase, strongly induced by hypoxia. CA IX is overexpressed by several cancer cells from many tumor types, and is a component of the pH regulatory system invoked by these cells to combat the deleterious effects of a high rate of glycolytic metabolism. CA IX functions to help produce and maintain an intracellular pH favorable for tumor cell growth and survival, while at the same time participating in the generation of an increasingly acidic extracellular space, facilitating tumor cell invasiveness (1).

Immunohistochemistry-Frozen: Carbonic Anhydrase IX Antibody

In addition to its role in the regulation of tumoral pH and tumor cell survival, there is evidence that CAIX contributes to cell processes such as adhesion and migration, both of which are vital for metastatic progression in human cancer. In CAIX-null MDCK cells constitutively expressing human CA IX, the protein localized to cell-cell junctions and overlapped with staining for E-cadherin as determined using anti-CAIX antibodies indicating that CAIX has the capacity to modulate E-cadherin-mediated cell adhesion via interaction with beta-catenin, which could be of potential significance in hypoxia-induced tumor progression (2). Expression of CA IX as determined by ant-CA IX antibodies has been correlated with poor prognosis in cancer and the metabolic dysfunction under the hypoxic conditions (3). Pharmacologic interference of CAIX catalytic activity using monoclonal antibodies or CAIX-specific small molecules has been shown to impair primary tumor growth and metastasis and is an open area of research. Novus Biologicals offers a wide variety of tools for your research needs in the form of antibodies, cell lysates and RNAi reagents against Carbonic Anhydrase IX and related proteins for your research needs.

  1. PMID: 22289741
  2. PMID: 14567991
  3. PMID: 19367501

Novus Biologicals offers Carbonic Anhydrase IX reagents for your research needs including:

Carbonic Anhydrase IX and Hypoxic Response: A Path to Tumors

Wednesday, November 30th, 2011

Carbonic Anhydrase IX (CA-IX) is an enzyme that is induced under hypoxic conditions. This enzyme is rarely present in normal cells and is responsible for controlling tumor pH. CA-IX is a transmembrane glycoprotein of the zinc metalloenzyme family. This family displays 15 isoforms in human tissues. Carbonic Anhydrase IX functions to convert carbonic acid present in hypoxic cells into a biocarbonate and a proton. Due to the hypoxic conditions found in many tumors CA-IX has become a marker of hypoxia and expression has been associated with several tumors such as lung, brain, colorectal, ovarian, renal, breast, and cervical to name a few.

Western Blot: Carbonic Anhydrase IX Antibody

Carbonic Anhydrase IX can be regulated through Hypoxia Inducible Factors. HIF proteins cause upregulation of the CA-IX gene to stabilize the microenvironment of tumor/hypoxic cells. The upregulation of the CA-IX gene is caused by Hypoxia Inducible Factor (HIF) undergoing specific hydroxylations dependent on oxygen conditions within the cell. Once the hydroxylation occurs HIF-1 alpha can interact with the beta domain on the Von Hippel-Lindau protein. In the presence of oxygen, HIF proteins will undergo rapid degradation. In the absence of oxygen, HIF can activate a signal cascade to transcribe several targets such as Carbonic Anhydrase IX. Since many tumors induce hypoxic conditions, CA-IX is being used as a marker. Studies are being performed to look at levels of hypoxia within certain tumors, as hypoxic tumors often are more aggressive and have a lower survival rate. Tan, E. Y., et al. [PMID: 19165203] suggested that CA-IX positive tumors may be due to an advanced hypoxic response and that continued research on the HIF pathway and targets regulated by this pathway such as CA-IX are pivotal in future cancer research.

Novus Biologicals offers CA-IX reagents for your research needs including: