Ectodomain shedding of the hypoxia-induced carbonic anhydrase IX is a metalloprotease-dependent process regulated by TACE/ADAM17
2005

How Carbonic Anhydrase IX is Shed from Tumor Cells

publication Evidence: moderate

Author Information

Author(s): Zatovicova M, Sedlakova O, Svastova E, Ohradanova A, Ciampor F, Arribas J, Pastorek J, Pastorekova S

Primary Institution: Center of Molecular Medicine, Institute of Virology, Slovak Academy of Sciences

Hypothesis

The shedding of carbonic anhydrase IX (CA IX) ectodomain is regulated by metalloproteases and influenced by hypoxia.

Conclusion

The study found that CA IX ectodomain shedding is a regulated process that responds to physiological factors and signal transduction stimuli.

Supporting Evidence

  • CA IX is a protein that is often found in high levels in cancer cells.
  • The study showed that the shedding of CA IX is sensitive to metalloprotease inhibitors.
  • Hypoxia increases the expression of CA IX in tumor cells.
  • Different cell lines showed varying levels of CA IX shedding.
  • BB-94, a metalloprotease inhibitor, significantly reduced CA IX shedding.

Takeaway

This study shows that a protein called CA IX, which is found in cancer cells, can be released into the surrounding area, and this process is controlled by certain enzymes and the amount of oxygen present.

Methodology

The researchers analyzed various cell lines for their ability to shed CA IX and used inhibitors to study the mechanisms involved.

Limitations

The study does not identify the specific metalloprotease responsible for the basal shedding of CA IX.

Digital Object Identifier (DOI)

10.1038/sj.bjc.6602861

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