UV-Induced Triggering of a Biomechanical Initiation Switch Within Collagen Promotes Development of a Melanoma-Permissive Microenvironment in the Skin
Abstract
The central objective of this proposal was to test the hypothesis that UV irradiation facilitates the exposure of the HU177 cryptic collagen epitope which may represent an early solid state biomechanical initiation switch that promotes inflammation, skin damage and the creation of a melanoma permissive niche. We made significant progress towards the overall goals of our proposal. Our current findings suggest that UVA and UVB dose dependently and differentially trigger conformational changes in collagen type-I and IV resulting in the exposure of the HU177 cryptic epitope. Given the differential exposure of the HU177 cryptic epitope following UV-irradiation, it is possible that distinct differences might be observed in the ability of different cell populations to attach to collagen following UVirradiation. Our findings indicated that while melanoma cell adhesion was generally enhance by 40% to 50% on collagen type-I and IV following UV-irradiation, fibroblast adhesion to collagen type-I was only minimally enhanced. In contrast, dramatic enhancement (5-fold) of macrophage adhesion to UVB irradiated collagen type-IV was observed while little change in adhesion was observed to UVB irradiated collage type-I. These studies suggest that distinct cell types exhibit different adhesive responses to UVA and UVB irradiated collagen type- I and -IV in vitro.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2011
- Accession Number
- ADA555980
Entities
People
- Peter C Brooks
Organizations
- Maine Medical Center