1 research outputs found
Use of a Tissue Engineered Human Skin Model to Investigate the Effects of Wounding and of an Anti-Inflammatory on Melanoma Cell Invasion
An increasing number of studies suggest inflammation stimulates tumour invasion. In melanoma,
despite recent advances in targeted therapy and immunomodulatory therapies, this
cancer remains difficult to treat. Our previous studies show melanoma cells interact with
skin cells in their invasion into tissue engineered skin and suggest inflammation stimulates
invasion. The aim of this study was to investigate the use of an anti-inflammatory on melanoma
invasion. To do this we developed a wounded and inflamed in vitro 3D melanoma
model in which to investigate the use of an anti-inflammatory on melanoma invasion. The
tissue engineered skin model was based on human de-epidermised acellular dermis to
which keratinocytes, fibroblasts and three different melanoma cell lines were added in various
combinations. A simple incisional wound was made in the model and TNF-α and fibrin
were added to simulate conditions of inflammation. Topical ibuprofen in a hydrogel was
added and the extent of melanoma invasion into the dermis was assessed under the various
conditions. The results showed that penetration of two of the cell lines (HBL and
A375SM) into the tissue engineered skin was exacerbated by wounding and ibuprofen significantly
decreased invasion of A375SM cells and slightly reduced invasion of HBL cells. A
third cell line, C8161, was aggressively invasive under all conditions to an extent that was
not influenced by wounding, TNF-α or the addition of ibuprofen. In summary, the results for
one these cell lines (and a trend for a second cell line) support the hypothesis that a wound
environment is conducive to melanoma invasion but the local addition of an anti-inflammatory
drug such as ibuprofen may attenuate invasion