Abstract
We demonstrate that a spatial and temporal analysis of subclinical hyperemia reliably predicts specific areas at high risk
for skin tumor development during photocarcinogenesis. To determine detailed spatiotemporal patterns of inflammatory
angiogenesis foci in a relatively large area, we developed a mesoscopic (between microscopic and macroscopic) imaging
approach. This method relies on our earlier finding that the combination of a spectral analysis of hemoglobin with
diffuse-light-suppressed imaging can increase the image resolution, contrast and penetration depth to visualize
microvasculature Hgb content in the large tissue area. In our recent study, SKH1 hairless albino mice were irradiated
for 10 weeks with a carcinogen dose of UVB. Using our newly developed mesoscopic imaging methods, we imaged
the mice over 20 - 30 weeks after stopping UVB, and excised hyperemic/non-hyperemic areas at several different timepoints.
We show that persistent hyperemic foci can predict future tumor formation. In particular, our imaging approach
allows us to assess the spatial and temporal extent of subclinical inflammatory foci, which in turn can predict sites of
future overlying tumor formation. In addition, although COX-2 inhibitors are known to suppress skin cancer
development in humans, it remains unclear whether the chemopreventive activity of COX-2 inhibitors are chiefly
attributable to their anti-inflammatory effects. Our study provides evidence that subclinical subepithelial inflammatory
foci occur prior to overt tumor formation, and that these areas are highly predictive for future tumor formation, that
celecoxib’s ability to suppress tumorigenesis is tightly linked to its ability to reduce the area of subclinical inflammatory
foci.
