Human basal cell carcinoma: the induction of anagen hair follicle differentiation.
Clin Exp Dermatol
; 45(3): 309-317, 2020 Apr.
Article
em En
| MEDLINE
| ID: mdl-31556145
ABSTRACT
BACKGROUND:
Consistent with cancer stem cell driven pattern of growth, human basal cell carcinomas (BCCs) demonstrate differentiation along hair follicle (HF) lineages.AIM:
To define the pattern of differentiation and therapeutic targets that promote BCC differentiation and therefore BCC cancer stem cell exhaustion.METHODS:
An alkaline phosphatase substrate kit was used to determine dermal papilla cells within the BCC stroma. Autonomous HF cycle-dependent gene expression was identified by analysis of the human homologues of a murine gene set (total 2289 genes) that is differentially expressed in hair cycle phases. The findings were validated by quantitative real-time PCR and immunofluorescence, as well as in vitro transforming growth factor (TGF)-ß2 stimulation of BCC cancer stem cell colonies.RESULTS:
As in the HF, keratin expression in the inner root sheath and matrix in BCC correlated with proliferative index and was tightly regulated, despite the absence of dermal papilla cells. Cross-species microarray analysis comparing human BCC and murine synchronous HF growth cycle datasets revealed 74% concordance with telogen differentiation compared with anagen (23%, P < 0.01) and catagen (49%; P < 0.01). Incomplete anagen differentiation within BCC was characterized by reduced expression of the anagen master regulator DLX3 (-5.5-fold), and increased expression of telogen-associated genes AEBP1 (2.2-fold), DEFB8 (35.3-fold), MMP3 (106.0-fold) and MMP12 (12.9-fold). Restoration of dermal papilla signals by in vitro addition of TGF-ß2 enhanced anagen differentiation.CONCLUSION:
Our findings show that BCC cells differentiate along HF lineages and may be susceptible to exogenous HF cycle modulators.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Cutâneas
/
Carcinoma Basocelular
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Diferenciação Celular
/
Folículo Piloso
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Clin Exp Dermatol
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Reino Unido