UV-Induced Triggering of a Biomechanical Initiation Switch within Collagen Promotes Development of a Melanoma-Permissive Microenvironment in the Skin
Annual rept. 1 Sep 2012-31 Aug 2013
MAINE MEDICAL CENTER PORTLAND
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The overall objective of our proposal was to test whether UV irradiation facilitates the exposure of the HU177 cryptic epitopes which may represent a solid state biomechanical initiation switch that promotes inflammation, skin damage and the creation of a melanoma permissive niche. Our new studies suggest that activated fibroblasts and mast cells are present within full thickness mouse and human skin and that fibroblasts accumulate in regions rich in basement membrane components after UV exposure. Interestingly, the exposure of subsets of the HU177 epitopes within the basement membrane preparation MatrigelTM depend in part, on the generation of reactive oxygen species. Surprisingly, while cell adhesion to UVB-irradiated MatrigelTM and collagen was higher than that to non-irradiated substrates, migration was significantly inhibited. Moreover, UVB-induced cell adhesion to irradiated substrates was not significantly altered by irradiation of these substrates in the presence of SOD suggesting that UVB-irradiation may cause exposure of a distinct subset of the HU177 epitopes as well as the exposure of additional non-HU177 cryptic sites that play distinct role in modulating cellular behavior. Collectively our new findings provide unique insight into the differential impact of UV irradiated ECM substrates have on the behavior of stromal and inflammatory cells.
- Medicine and Medical Research