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Actinic keratosis modelling in mice: A translational study
Arnaud Pillon1, Bruno Gomes1, Isabelle Vandenberghe1
1Pierre Fabre Research Institute, Research & Development Center, Toulouse, France.
Background:
Actinic keratoses (AK) are pre-malignant cutaneous lesions caused by prolonged exposure to ultraviolet radiation. As AKs lesions are generally accepted to be the initial lesions in a disease continuum that progresses to squamous cell carcinoma (SCC), AK lesions have to be treated. They are also the second most common reason for visits to the dermatologist. Several treatments are available but their efficacy still needs to be improved. The UV-B-induced KA lesion mouse model is used in preclinical studies to assess the efficacy of novel molecules, even though it is often more representative of advanced AK or SCC.
Objectives:
Here we report on a translational study, comparing the various stages of AK development in humans and in the UV-B irradiated mouse model, as well as the optimization of photograph acquisition of AK lesions on mouse skin.
Methods:
Human and mouse skin lesions were analysed by histology and immunohistochemistry. Mouse lesions were also assessed using a digital dermatoscope.
Results:
An histological and phenotypic analysis, including p53, Ki67 and CD3 expression detection, performed on human and mouse AK lesions, shows that overall AK modelling in mice is relevant in the clinical situation. Some differences are observed, such as disorganization of keratinocytes of the basal layer and a number of atypical nuclei which are more numerous in human AK, whereas much more pronounced acanthosis is observed in skin lesion in mice. Thanks to this translational study, we are able to select appropriate experimental conditions for establishing either early or advanced stage AK or an SCC model. Furthermore, we optimized photograph acquisition of AK lesions on mouse skin by using a digital dermatoscope which is also used in clinics and allows reproducible photograph acquisition for further reliable assessment of mouse lesions. Use of this camera is illustrated through a pharmacological study assessing the activity of CARAC®.
Conclusion:
These data demonstrate that this mouse model of UV-B-induced skin lesions is predictive for the identification of novel therapeutic treatments for both early and advanced stages of the disease.
Insights
This study validates a UV-B-induced mouse model for actinic keratosis (AK) and squamous cell carcinoma (SCC) development. The model accurately predicts therapeutic treatments for early and advanced skin lesions.
Area of Science:
- Dermatology
- Preclinical Research
- Cancer Biology
Background:
- Actinic keratoses (AK) are pre-malignant skin lesions progressing to squamous cell carcinoma (SCC).
- Current AK treatments require efficacy improvement.
- UV-B-induced mouse models are used for preclinical AK/SCC studies.
Purpose of the Study:
- To compare human and UV-B-induced mouse AK lesion development.
- To optimize photographic assessment of mouse AK lesions.
- To validate a mouse model for predicting therapeutic efficacy.
Main Methods:
- Histological and immunohistochemical analysis of human and mouse AK lesions.
- Assessment of mouse lesions using digital dermoscopy.
- Optimization of digital dermoscopy for reproducible imaging.
Main Results:
- Mouse AK models show histological and phenotypic similarities to human lesions.
- Differences in keratinocyte disorganization and acanthosis were noted.
- Optimized digital dermoscopy enables reliable assessment and selection of experimental conditions.
Conclusions:
- The UV-B-induced mouse model is relevant for studying AK and SCC.
- This model can predict novel therapeutic treatments for early and advanced skin lesions.
- Optimized imaging enhances the model's utility in preclinical research.
