Abstract
Although several studies propose a chemopreventive effect of aspirin for colorectal cancer (CRC) development, the general use of aspirin cannot be recommended due to its adverse side effects. As the protective effect of aspirin has been associated with an increased expression of COX-2, molecular imaging of COX-2, for instance, during confocal endomicroscopy could enable the identification of patients who would possibly benefit from aspirin treatment. In this pilot trial, we used a COX-2-specific fluorescent probe for detection of colitis-associated and sporadic CRC in mice using confocal microscopy. Following the injection of the COX-2 probe into tumor-bearing APCmin mice or mice exposed to the AOM + DSS model of colitis-associated cancer, the tumor-specific upregulation of COX-2 could be validated with in vivo fluorescence imaging. Subsequent confocal imaging of tumor tissue showed an increased number of COX-2 expressing cells when compared to the normal mucosa of healthy controls. COX-2-expression was detectable with subcellular resolution in tumor cells and infiltrating stroma cells. These findings pose a proof of concept and suggest the use of CLE for the detection of COX-2 expression during colorectal cancer surveillance endoscopy. This could improve early detection and stratification of chemoprevention in patients with CRC.
Highlights
A growing amount of evidence highlights the role of the acetylsalicylate aspirin for the chemoprevention of sporadic colorectal cancer (CRC) [1,2,3,4]
As the protective effect of aspirin has been associated with an increased expression of COX-2, molecular imaging of COX-2, for instance, during confocal endomicroscopy could enable the identi cation of patients who would possibly bene t from aspirin treatment
Whereas nearly no COX2 expressing cells were visible in healthy colon specimens, some COX-2 positive cells could be detected in the lamina propria of in amed non-neoplastic colon tissue of AOM dextran sodium sulfate (DSS)-treated mice
Summary
A growing amount of evidence highlights the role of the acetylsalicylate aspirin for the chemoprevention of sporadic colorectal cancer (CRC) [1,2,3,4] Aminosalicylates such as sulfasalazine, mesalazine, and others have been shown to reduce the risk for colitis-associated colorectal cancer (CAC) in patients with in ammatory bowel disease [5]. Ese data propose the use of COX-inhibiting agents for the prevention of sporadic CRC and CAC. The inhibition of COX enzymes is associated with severe side effects in treated patients [11] In this regard, it would be helpful to quantify COX-2 activity in healthy, in amed, or dysplastic colonic tissue in order to identify patients that could bene t from the treatment with COX inhibitors as a preventive or therapeutic strategy
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