Abstract 3164: Inflammasomes: fanning the flames of malignant mesothelioma initiation

Malignant mesothelioma (MM) is an aggressive and devastating cancer of the pleural/peritoneal mesothelium related to asbestos exposure. MM has a low survival rate (average: less than 12 months). Despite the causal relationship between asbestos and MM development, the exact mechanism by which asbestos causes MM is still poorly understood. There is an urgent need for the identification of mechanism(s) that may help in early detection and finding new treatment targets for prevention and treatment of MM.We have recently shown that asbestos exposure of human mesothelial cells (HMCs) leads to the activation of the NLRP3 inflammasome and a concomitant increase in the secretion of the inflammasome products, IL-1β and IL-18. Other studies have shown that IL-1β promotes the stemness of colon cancer cells and an epithelial to mesenchymal transition (EMT) of corneal endothelial cells. The activation of the inflammasome by asbestos is protracted in mesothelial cells and led us to hypothesize that the inflammasome and its products play a crucial role in the tumorigenesis of MM by promoting a mesothelial to fibroblastic transition (MFT) of HMCs. Our studies using EMT PCR array revealed that asbestos exposure results in the down regulation of E-cadherin and KRT19 among others in HMCs. Western blot analysis revealed decreases in expression of the epithelial markers, E-cadherin, Claudin-1 and β-catenin in response to asbestos exposure, while levels of the transcription factors ZEB-1, Snail ...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Immunology Source Type: research