Topical tamoxifen--a potential therapeutic regime in treating excessive dermal scarring?

Abstract

Abnormal dermal scarring which affects a large number of people is aesthetically disfiguring and can be functionally disabling. Existing medical and surgical strategies to prevent or to treat scars are frequently disappointing and more effective therapies are needed. Tamoxifen, which has been used extensively in the treatment of breast cancer over the last 20 years has recently been shown to inhibit the proliferation of fibroblasts cultured from keloid biopsies. Successful treatment of retroperitoneal fibrosis and desmoid tumours with tamoxifen has also been reported. We have investigated the potential of tamoxifen as an inhibitor of wound contraction, using fibroblast-populated collagen lattices as an in vitro model. From these studies we postulate that tamoxifen may have potential clinical significance in the treatment of abnormal scarring. Normal adult human skin fibroblasts were embedded within type I collagen, then medium either with or without addition of tamoxifen was added to the collagen lattices. Lattice diameters were measured at intervals to assess the influence of tamoxifen on the lattice contraction. The reversibility of the inhibitory effect of tamoxifen on lattice contraction was investigated by 'washing out the tamoxifen' at different time-points. To visualise changes in the morphology of fibroblasts MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] was added to the lattices. Tamoxifen at 1 and 5 microM had no significant influence on lattice contraction but higher concentrations of 50 and 100 microM completely inhibited contraction. At intermediate concentrations from 10 to 20 microM the degree of lattice contraction was dose-dependent. The reversibility of the inhibition was both dose- and time-dependent. Both the inhibition of contraction and the reversibility of inhibition appeared to correlate with changes in fibroblast morphology. The dose- and time-dependent inhibition of contraction by fibroblasts suggests that tamoxifen could be investigated as a novel potential therapeutic agent in treating abnormal dermal scarring.