1. The TRPA1 Channel Amplifies the Oxidative Stress Signal in Melanoma
- Author
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Romina Nassini, Luigi Francesco Iannone, Lorenzo Landini, Margherita Vannucchi, Mustafa Titiz, Daniela Massi, Daniel Souza Monteiro de Araujo, Vincenzo De Giorgi, Pierangelo Geppetti, Francesco De Logu, Filippo Ugolini, and Francesca Portelli
- Subjects
Adult ,Male ,Adolescent ,QH301-705.5 ,Antigens, Differentiation, Myelomonocytic ,chemistry.chemical_element ,Calcium ,medicine.disease_cause ,Models, Biological ,TRPA1 ,Article ,Young Adult ,Transient receptor potential channel ,Antigens, CD ,image analysis ,Cell Line, Tumor ,Tumor-Associated Macrophages ,medicine ,melanoma ,Animals ,Humans ,Gene silencing ,Ankyrin ,oxidative stress ,Biology (General) ,Child ,Nevus ,TRPA1 Cation Channel ,Aged ,Respiratory Burst ,Aged, 80 and over ,chemistry.chemical_classification ,Aldehydes ,Reactive oxygen species ,Chemistry ,Melanoma ,food and beverages ,Dermis ,General Medicine ,Middle Aged ,medicine.disease ,macrophages ,HEK293 Cells ,Cancer research ,Female ,Carcinogenesis ,Oxidative stress ,psychological phenomena and processes - Abstract
Macrophages (MΦs) and reactive oxygen species (ROS) are implicated in carcinogenesis. The oxidative stress sensor, transient receptor potential ankyrin 1 (TRPA1), activated by ROS, appears to contribute to lung and breast cancer progression. Although TRPA1 expression has been reported in melanoma cell lines, and oxidative stress has been associated with melanocytic transformation, their role in melanoma remains poorly known. Here, we localized MΦs, the final end-product of oxidative stress, 4-hydroxynonenal (4-HNE), and TRPA1 in tissue samples of human common dermal melanocytic nevi, dysplastic nevi, and thin (pT1) and thick (pT4) cutaneous melanomas. The number (amount) of intratumoral and peritumoral M2 MΦs and 4-HNE staining progressively increased with tumor severity, while TRPA1 expression was similar in all samples. Hydrogen peroxide (H2O2) evoked a TRPA1-dependent calcium response in two distinct melanoma cell lines (SK-MEL-28 and WM266-4). Furthermore, H2O2 induced a TRPA1-dependent H2O2 release that was prevented by the TRPA1 antagonist, A967079, or Trpa1 gene silencing (siRNA). ROS release from infiltrating M2 MΦs may target TRPA1-expressing melanoma cells to amplify the oxidative stress signal that affects tumor cell survival and proliferation.
- Published
- 2021
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