Chemotherapy targets the hair-follicle vascular network but not the stem cells.
Chemotherapy-induced alopecia is a major problem in clinical oncology. Doxorubicin, a widely used cancer chemotherapy drug, induces disruption of the hair cycle and subsequent alopecia. We show in this report that doxorubicin causes disruption of the hair-follicle-associated blood vessel network resulting in a greatly reduced density of these blood vessels. Dystrophic hair follicles were also observed with abnormal melanogenesis in the mice treated with doxorubicin. Visualization of the effect of doxorubicin on hair-follicle angiogenesis was made possible by the use of transgenic mice in which green fluorescent protein was driven by regulatory elements of the nestin gene (ND-GFP). In these transgenic mice, the hair-follicle stem cells and the follicle structure as well as the blood vessels associated with the hair follicles express ND-GFP. The hair-follicle stem cells did not appear to be affected by doxorubicin, which may explain why hair regrows after chemotherapy. These results suggest that inhibition of hair-follicle-associated angiogenesis by doxorubicin may be an important factor in hair-follicle dystrophy associated with chemotherapy-induced alopecia. The ND-GFP mouse model is thus useful for the study of the role of angiogenesis in the hair-follicle cycle and the effect of drugs on processes associated with chemotherapy-induced alopecia.
Amoh
Yasuyuki
Y
AntiCancer Inc., San Diego, California 92111, USA.
Li
Lingna
L
Katsuoka
Kensei
K
Hoffman
Robert M
RM
D000505:Alopecia / Q000139:chemically induced*; D000818:Animals; D004317:Doxorubicin / Q000633:toxicity*; D049452:Green Fluorescent Proteins / Q000235:genetics; D018859:Hair Follicle / Q000098:blood supply* / Q000166:cytology / Q000187:drug effects; D007381:Intermediate Filament Proteins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000235:genetics; D064231:Nestin; D013234:Stem Cells / Q000187:drug effects*
D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D049452:Green Fluorescent Proteins; D004317:Doxorubicin