Keratinocyte growth factor increases hair follicle survival following cytotoxic insult

Abstract

Hair loss is a distressing side-effect of cancer therapy. Factors that might reduce this loss are therefore likely to improve patient well-being and reduce treatment refusal. Keratinocyte growth factor has been shown to regulate proliferation and differentiation in epithelial tissues and may regulate the clonogenic cells (stem cells) of the hair follicle. Using X- irradiation as a model cytotoxic agent we investigated whether keratinocyte growth factor pretreatment could increase hair follicle survival (by implication clonogen survival) and regeneration of differentiated progeny (a hair). Irradiated telogen follicle survival data were consistent with that published previously. Daily keratinocyte growth factor pretreatment increased hair survival during the first hair growth cycle, the level of protection having a slight radiation dose dependence. Protection was maintained after a second hair cycle, but at a lower level (hairs and follicles). Hairs irradiated in anagen and analyzed during the second cycle exhibited a similar level of protection. No difference in protection levels could be observed between mice treated either once or twice daily with keratinocyte growth factor. Results indicated approximately 10 extra hairs per mm2 (14.5% of unirradiated control) could survive the cytotoxic insult if pretreated with 12.5 μg keratinocyte growth factor. This could be doubled by a 10 X higher keratinocyte growth factor dose. The fact that protection was maintained during two cycles of hair growth indicated that the clonogenic cells had been protected. Keratinocyte growth factor pretreatment had no significant effect on the level of mitosis but increased the number of p21(waf1) expressing cells. Intriguingly, the number of apoptotic fragments per follicle were transiently increased in the keratinocyte growth factor pretreated mice, although this effect was most pronounced in the upper half of the follicle bulb, i.e., above (rather than within) the germinal matrix.