Effects of photodynamic therapy on dermal fibroblasts from xeroderma pigmentosum and Gorlin-Goltz syndrome patients

// Alicia Zamarron 1 , Marta Garcia 2, 3, 4 , Marcela Del Rio 2, 3, 4 , Fernando Larcher 2, 3, 4 and Angeles Juarranz 1 1 Department of Biology, Faculty of Sciences, Autonoma University of Madrid, IRYCIS, Madrid, Spain 2 Department of Bioengineering, Carlos III University (UC3M), Madrid, Spain 3 CIEMAT-Centro de Investigaciones Biomedicas en Red de Enfermedades Raras (CIBERER), Madrid, Spain 4 Instituto de Investigacion Sanitaria de la Fundacion Jimenez Diaz (IIS-FJD), Madrid, Spain Correspondence to: Angeles Juarranz, email: angeles.juarranz@uam.es Fernando Larcher, email: fernando.larcher@ciemat.es Keywords: photodynamic therapy, ultraviolet light, cancer-associated fibroblasts, Gorlin-Goltz syndrome, xeroderma pigmentosum Received: May 10, 2017      Accepted: July 26, 2017      Published: August 24, 2017 ABSTRACT PDT is widely applied for the treatment of non-melanoma skin cancer pre-malignant and malignant lesions (actinic keratosis, basal cell carcinoma and in situ squamous cell carcinoma). In photodynamic therapy (PDT) the interaction of a photosensitizer (PS), light and oxygen leads to the formation of reactive oxygen species (ROS) and thus the selective tumor cells eradication. Xeroderma pigmentosum (XP) and Gorlin-Goltz Syndrome (GS) patients are at high risk of developing skin cancer in sun-exposed areas. Therefore, the use of PDT as a preventive treatment may constitute a very promising therapeutic modality for these syndromes. Given the demonstrated role of cancer associated fibroblasts (CAFs) in tumor progression and the putative CAFs features of some cancer-prone genodermatoses fibroblasts, in this study, we have further characterized the phenotype of XP and GS dermal fibroblasts and evaluated their response to methyl-δ-aminolevulinic acid (MAL)-PDT compared to that of dermal fibroblasts obtained from healthy donors. We show here that XP/GS fibroblasts display clear features of CAFs and present a significantly higher response to PDT, even after being stimulated with UV light, underscoring the value of this therapeutic approach for these rare skin conditions and likely to other forms of skin cancer were CAFs play a major role.