Caveolin-1 is expressed on multipotent cells of hair follicles and might be involved in their resistance to chemotherapy.
BACKGROUND
Caveolin-1 is the principal protein that composes caveolae, which are vesicular invaginations present on the plasma membrane of different cell types. Caveolae are involved in a variety of cellular functions including regulation of proliferation rate and resistance to chemotherapeutic drugs. Chemotherapy frequently induces alopecia which is reversible most probably due to the low proliferative rate of hair follicle stem cells and due to the expression of proteins which confer resistance.


OBJECTIVE
Using a specific animal model and immunohistochemistry, we analysed the expression of both caveolin-1 and the cell proliferation marker beta-catenin, at different stages of the hair follicle cycle, both before and after doxorubicin (DXR) -induced alopecia.


METHODS
Seven-week-old C57BL/6 mice were depilated in order to synchronize hair follicle cycle in the anagen phase. Chemotherapy with DXR 15 mg kg(-1) was used to induce alopecia. Control and treated mice were then sacrificed at precise time points and caveolin-1 expression in hairs at different stages of the cycle were analysed by immunohistochemistry. By double immunofluorescence, colocalization of caveolin-1 and cytokeratin-15 was confirmed in the bulge region. The state of proliferation of cells composing hair follicle was assessed by beta-catenin immunohistochemistry.


RESULTS
Caveolin-1 was expressed by the cells of the bulge area, the multipotent compartment of the hair follicle, during all phases of growth (anagen), regression (catagen) and resting (telogen). During the anagen phases, nuclear beta-catenin labelling was not observed in bulge cells, but rather in the deeper portion of the follicle. Damaged hair follicles from DXR-treated mice presented bulge cells which still expressed caveolin-1, suggesting that this protein might play a role in their drug resistance. As expected, no beta-catenin nuclear staining was detectable in DXR-treated hair follicles, indicating the complete lack of proliferative processes. The differential localization of caveolin-1 and beta-catenin suggests that the mutually exclusive expression of these proteins is useful for correct hair regrowth, whether during the physiological cycle or after chemotherapy-induced alopecia.


CONCLUSIONS
Expression of caveolin-1 within the multipotent cell compartment of the hair follicle can explain the resistance of bulge cells to many chemotherapeutics, suggested by the reversibility of chemotherapy-induced alopecia.
Selleri
S
S
Department of Human Morphology, National Cancer Institute, Università degli Studi di Milano, Via Mangiagalli, 31, 20133 Milan, Italy.
Arnaboldi
F
F
Palazzo
M
M
Hussein
U
U
Balsari
A
A
Rumio
C
C
D000505:Alopecia / Q000139:chemically induced / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects; D015415:Biomarkers / Q000032:analysis; D051242:Caveolin 1; D022461:Caveolins / Q000032:analysis* / Q000378:metabolism; D049109:Cell Proliferation; D003598:Cytoskeletal Proteins / Q000032:analysis; D004317:Doxorubicin / Q000009:adverse effects; D004351:Drug Resistance; D018859:Hair Follicle / Q000473:pathology*; D006204:Hair Removal; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D039902:Multipotent Stem Cells / Q000187:drug effects / Q000378:metabolism*; D015534:Trans-Activators / Q000032:analysis; D051176:beta Catenin
D000970:Antineoplastic Agents; D015415:Biomarkers; C495267:CTNNB1 protein, mouse; C495541:Cav1 protein, mouse; D051242:Caveolin 1; D022461:Caveolins; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin; D004317:Doxorubicin