UV-Induced Triggering of a Biomechanical Initiation Switch Within Collagen Promotes Development of a Melanoma-Permissive Microenvironment in the Skin
Annual rept. 1 Sep 2011-31 Aug 2012
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 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. Our current studies suggest that UV-mediated structural alterations in collagen type-I, collagen type-IV and Matrigel trademark differentially alter the ability of human melanoma cells, human dermal fibroblasts and macrophages to attach, migrate and proliferate on these ECM substrates. These in vitro results are consistent with the possible ability of UV-irradiation of ECM proteins to differentially alter the response of distinct subsets of tumor and normal stromal cells to ECM proteins that help compose the skin microenvironment. In addition, our new data suggest that pre-treating mice with anti-HU177 antibody inhibited UVB-induced accumulation of mast cells in the skin. Moreover, pre-treating mice with a single dose of anti-HU177 antibody also reduced the UVassociated increase in tumor growth by nearly 40. Taken together, these new data suggest a functional role the HU177 collagen epitope in UV-enhanced inflammation and tumor growth in vivo.
- Anatomy and Physiology
- Medicine and Medical Research