Cell reports · 2025
Injury and inflammation promote cancer progression at the anorectal junction.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
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Petitpas Chloé, Mitoyan Louciné, Thevin Valentin, Martin Marjorie, Hernandez-Vargas Hector, Chevrier Véronique, Ollivier Alexane, Kaya Muge, Poizat Flora, Heinisch Marie, Rodrigues Magda, Gameiro-Ferreira Laetitia, Ratone Jean-Philippe, Caillol Fabrice, Dahel Yanis, Hoibian Solène, Giovannini Marc, de Chaisemartin Cécile, Charafe-Jauffret Emmanuelle, Ginestier Christophe, Marie Julien C, Guasch Géraldine
Аннотация
In anorectal cancer, epithelial tumors frequently develop in transition zones (TZs) between the anal and the rectal epithelia, a region subjected to inflammation and wounds. However, whether inflammation and wounds contribute to tumor development in the anorectal region remain totally unknown. Using mice with KRASG12D mutation selectively at the TZ cells, we found that recurrent wound and its associated sustained inflammation are essential to promote tumor development. We characterized at the single-cell level the malignant events that occurred at the TZ all along tumor development from early neoplastic, hyperplastic, to malignant transition. We showed that this tumoral development was under the influence of interleukin (IL)-17, a cytokine highly secreted by a γδ T lymphocyte subset, allowing the recruitment of neutrophils at the TZ, which was crucial for tumor progression. Hence, this study reveals the importance of wound and its associated IL-17/neutrophil inflammatory axis in cancer progression.