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.
Highlights
Ultraviolet radiation (UVR) from sun is the major etiologic factor responsible for skin cancer
Xeroderma pigmentosum (XP) is a rare, autosomal, recessive, genetic disorder that occurs as a result of mutations in genes involved in the nucleotide excision repair www.impactjournals.com/oncotarget (NER) pathway, making defective the responses of XP cells to photoproducts induced in DNA by UVR from sunlight
To characterize the putative cancer associated fibroblasts (CAFs) features of fibroblasts obtained from XP and Goltz Syndrome (GS) donors, we evaluated the protein expression pattern (Figure 1A) and the intensity of the fluorescent signal (Figure 1B) of α-sma, vinculin/Factin, vimentin and endoglin by immunofluorescence
Summary
Ultraviolet radiation (UVR) from sun is the major etiologic factor responsible for skin cancer. Xeroderma pigmentosum (XP) is a rare, autosomal, recessive, genetic disorder that occurs as a result of mutations in genes involved in the nucleotide excision repair www.impactjournals.com/oncotarget (NER) pathway, making defective the responses of XP cells to photoproducts induced in DNA by UVR from sunlight. Patients with this syndrome have a very high predisposition for developing skin cancers in sun-exposed areas due to this diminished DNA repair activity [2, 5, 6]. Most mutations occur in Patched (PTCH 1) gene, can occur in Smoothened (SMO) gene [7,8,9,10]
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