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Research Paper
Detecting Changes in Tumor Hypoxia with Carbonic Anhydrase IX and Pimonidazole
Kyung Hwan Shin, Juan A Diaz-Gonzalez, James Russell, Qing Chen, Paul Burgman, Xiao-Feng Li and C. Cliffton Ling
volume 6 | issue 1
January 2007Pages: 70 - 75
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We have used immunohistochemistry to examine the dynamics of tumor hypoxia. Expression of CAIX is known to be influenced by tumor hypoxia, and this protein has been shown to be an endogenous hypoxia marker in several models. However, due to its long half-life, it could also be present in oxygenated tissue that had recently been hypoxic. To investigate this issue we have compared CAIX expression to the exogenous hypoxia marker, pimonidazole using HT29 (human colorectal cancer) xenografts. We manipulated tumor hypoxia with carbogen and hydralazine, treatments that respectively increased and decreased tumor oxygenation. (Carbogen was given 75 minutes and hydralazine 30 minutes before sacrifice) In tumors from the control group, CAIX and pimonidazole exhibited similar (though not identical) spatial distribution, and for both markers, the fraction of the section staining positively was similar (13.2% and 12.6% respectively). The mice treated with hydralazine showed a significant increase in pimonidazole accumulation (37.2%, P = 0.03), though the CAIX positive fraction was unchanged (14.2%). In contrast, in the carbogen group pimonidazole staining decreased to 3% (P = 0.01) though CAIX expression was again unaltered. These results suggest that comparison of CAIX and pimonidazole will allow for the detection of reoxygenation.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.