Ex Vivo Analysis of Cell Differentiation, Oxidative Stress, Inflammation, and DNA Damage on Cutaneous Field Cancerization. in International journal of molecular sciences / Int J Mol Sci. 2024 May 26;25(11):5775. doi: 10.3390/ijms25115775.
2024
AOU Novara
Tipo pubblicazione
Journal Article
Autori/Collaboratori (6)Vedi tutti...
Camillo L
Department of Health Sciences, University of Eastern Piedmont, Via Paolo Solaroli 17, 28100 Novara, Italy.
Zavattaro E
Department of Health Sciences, University of Eastern Piedmont, Via Paolo Solaroli 17, 28100 Novara, Italy.
Veronese F
AOU Maggiore della Carità di Novara, c.so Mazzini 18, 28100 Novara, Italy.
et alii...
Abstract
Cutaneous field cancerization (CFC) refers to a skin region containing mutated cells' clones, predominantly arising from chronic exposure to ultraviolet radiation (UVR), which exhibits an elevated risk of developing precancerous and neoplastic lesions. Despite extensive research, many molecular aspects of CFC still need to be better understood. In this study, we conducted ex vivo assessment of cell differentiation, oxidative stress, inflammation, and DNA damage in CFC samples. We collected perilesional skin from 41 patients with skin cancer and non-photoexposed skin from 25 healthy control individuals. These biopsies were either paraffin-embedded for indirect immunofluorescence and immunohistochemistry stain or processed for proteins and mRNA extraction from the epidermidis. Our findings indicate a downregulation of p53 expression and an upregulation of Ki67 and p16 in CFC tissues. Additionally, there were alterations in keratinocyte differentiation markers, disrupted cell differentiation, increased expression of iNOS and proinflammatory cytokines IL-6 and IL-8, along with evidence of oxidative DNA damage. Collectively, our results suggest that despite its outwardly normal appearance, CFC tissue shows early signs of DNA damage, an active inflammatory state, oxidative stress, abnormal cell proliferation and differentiation.
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PMID : 38891963
DOI : 10.3390/ijms25115775
Keywords
Humans; Oxidative Stress; DNA Damage; Cell Differentiation; Skin Neoplasms/metabolism/pathology/genetics; Inflammation/metabolism/genetics/pathology; Male; Female; Middle Aged; Ultraviolet Rays/adverse effects; Aged; Keratinocytes/metabolism/pathology; Nitric Oxide Synthase Type II/metabolism/genetics; Adult; Tumor Suppressor Protein p53/metabolism/genetics; Skin/metabolism/pathology/radiation effects; Ki-67 Antigen/metabolism/genetics; Cyclin-Dependent Kinase Inhibitor p16/metabolism/genetics; Interleukin-6/metabolism/genetics; DNA damage; field cancerization; oxidative stress; skin cancer; ultraviolet light;