Mechanisms of Asbestos Carcinogenesis

作者：Giovanni Gaudino, Haining Yang · 年份：2024 · DOI：10.1201/9781003431909-5 · 被引用次数：1 · 研究领域：Occupational and environmental lung diseases

Chronic inflammation induced by asbestos causes the release of cytokines, including high mobility group box 1 protein (HMGB1), tumor necrosis factor alpha, interleukin 1β, and IL-6, IL-8 that promote a pro-inflammatory microenvironment at fiber deposition sites, enabling human mesothelial cells (HMs) damaged by asbestos to evade cell death and, occasionally over the course of many years, give rise to mesothelioma, the type of cancer characteristically associated to asbestos exposure. Iron content within asbestos bodies may also promote carcinogenesis through facilitating chronic inflammation. HMs exposed to asbestos undergo programmed cell necrosis and release HMGB1, a damage-associated molecular pattern (DAMP) that fosters and sustains chronic inflammation along with the formation of the NLRP3 inflammasome. HMGB1 release upon asbestos exposure also triggers autophagy that enhances HM survival, which further promotes HM transformation. Mesothelial HMGB1 knockout mice validate these findings, showcasing HMGB1&s;s role in regulating inflammation and influencing mesothelioma development, progression, and animal survival. The development of mesothelioma is influenced by intricate interactions between genes and environmental factors. Chromothripsis pattern has been identified in mesothelioma and may play a key role in malignant transformation. Tumor suppressors that are commonly mutated in mesothelioma include BAP1, p16INK4a, p14ARF, and NF2/Merlin. Germline mutations of BAP1, a m...