Peer-reviewed veterinary case report
How does COX-2 affect cancer in dogs and cats?
By Heller, David A et al.·Published in Journal of veterinary internal medicine·2007·University of Illinois at Urbana-Champaign, United States·View original on PubMed →
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Original publication title: In vitro cyclooxygenase-2 protein expression and enzymatic activity in neoplastic cells.
Plain-English summary
This study looked at how well different tests can detect a protein called COX-2, which is linked to cancer, in certain cell lines. Researchers found that one test, called immunohistochemistry (IHC), sometimes gave misleading results, showing COX-2 when it wasn't actually present. In some cases, even when COX-2 was detected, it didn't mean that the cells were producing the related substance, prostaglandin E2 (PGE2), which is important for understanding how active the COX-2 protein is. The findings suggest that relying on IHC alone to decide on treatments for tumors in pets might not be the best approach, and using a more accurate test called Western blot could be better. Overall, the study indicates that current methods for assessing COX-2 in tumors may need to be re-evaluated.
Abstract
BACKGROUND: Cyclooxygenase-2 (COX-2) and its principle enzymatic metabolite, prostaglandin E2 (PGE2), are implicated in cancer progression. Based upon immunohistochemical (IHC) evidence that several tumor types in animals overexpress COX-2 protein, COX-2 inhibitors are used as anticancer agents in dogs and cats. HYPOTHESIS: IHC is inaccurate for assessing tumor-associated COX-2 protein and enzymatic activity. METHODS: Five mammalian cell lines were assessed for COX-2 protein expression by IHC and Western blot analysis (WB), and functional COX-2 activity was based upon PGE2 production. RESULTS: Detection of COX-2 protein by IHC and WB were in agreement in 4 of 5 cell lines. In 1 cell line that lacked COX-2 gene transcription because of promoter hypermethylation (HCT-116), IHC produced false-positive staining for COX-2 protein expression. Functional COX-2 enzymatic activity was dissociated from relative IHC-based COX-2 protein expression in 2 cell lines (RPMI 2650 and SCCF1). The RPMI 2650 cell line demonstrated strong COX-2 protein expression but minimal PGE2 production. CONCLUSIONS AND CLINICAL IMPORTANCE: Western blot is more accurate than IHC for the detection of COX-2 protein in the cell lines studied. Furthermore, the semiquantitative identification of COX-2 protein by IHC or WB does not necessarily correlate with enzymatic activity. Based upon the potential inaccuracy of IHC and dissociation of COX-2 protein expression from enzymatic activity, the practice of instituting treatment of tumors with COX-2 inhibitors based solely on IHC results should be reconsidered.
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Search related cases →Original publication on PubMed: https://pubmed.ncbi.nlm.nih.gov/17939563/