Epithelium–mesenchyme compartment interaction and oncosis on chemotherapy-induced hair damage

Abstract

It is known that chemotherapy induces alopecia in humans, with important psychological and social implications in spite of its reversibility. Among chemotherapeutic drugs, anthracyclines are widely used, yet cause severe alopecia. One of the causes for the elevated sensibility of hair follicles to anthracyclines, and to drugs in general, is the high proliferation rate of follicular epithelium and the long duration of the growth phase (up to 7 years in humans). To clarify the mechanism of anthracycline toxicity, we used a rat model and focused our attention on the morphological alterations in hair follicles induced by doxorubicin. We observed the progression of hair follicle degeneration in the epithelial and mesenchymal compartments until alopecia arose, by both light and electron microscopy. As a first sign of damage, significant apoptosis was detected in the proximal perifollicular connective tissue sheath and sporadically in the matrix, near the interface between matrix and follicular papilla. We propose the apoptotic remodeling of the mesenchymal compartment as a process that is fundamental to the progression of events leading to alopecia. Regarding the epithelial compartment, it is important to note that oncosis was observed in a large number of follicular cells in the outer root sheath during the last stages of hair follicle regression. This indicates that oncosis is involved in a major way in the damage of epithelial cells.

Oncosis: An important non-apoptotic mode of cell death

“…Our preliminary findings as well as reports in the literature (Selleri et al, 2004) show doxorubicin to induce at least two forms of cell injury leading to death: apoptosis and oncosis (Fig. 3).…”

Caveolin-1 is expressed on multipotent cells of hair follicles and might be involved in their resistance to chemotherapy

“…In this paper, using an appropriate animal model, we studied the expression of caveolin-1 during the different stages of the hair follicle life cycle, both before and after chemotherapy-induced alopecia. 20,21 We observed caveolin-1 expression within the bulge region of the hair follicle and we suggest that caveolae might be involved in stem cell survival during chemotherapy, subsequently allowing follicle regrowth.…”

“…No data are yet available for caveolin expression in the hair follicle. In this paper, using an appropriate animal model, we studied the expression of caveolin‐1 during the different stages of the hair follicle life cycle, both before and after chemotherapy‐induced alopecia 20,21 …”

Daunomycin accumulation and induction of programmed cell death in rat hair follicles

“…Although the present data cannot be immediately associated with studies of alopecia involving the drugs, they should contribute to our understanding of the way that these drugs interact with the hair follicle as a refined miniorgan, the life cycle of which depends upon a complex series of interactions between the epithelial and mesenchymal compartments (Tobin et al 2003;Selleri et al 2004).…”