1 research outputs found
Human basal cell carcinoma: the induction of anagen hair follicle differentiation
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 cycleâdependent 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 realâtime PCR and immunofluorescence, as well as in vitro transforming growth factor (TGF)âβ2 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. Crossâspecies 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 (â5.5âfold), and increased expression of telogenâassociated genes: AEBP1 (2.2âfold), DEFB8 (35.3âfold), MMP3 (106.0âfold) and MMP12 (12.9âfold). Restoration of dermal papilla signals by in vitro addition of TGFâβ2 enhanced anagen differentiation.
Conclusion
Our findings show that BCC cells differentiate along HF lineages and may be susceptible to exogenous HF cycle modulators