TMT-based quantitative proteomic analysis reveals the underlying mechanisms of glycidyl methacrylate-induced 16HBE cell malignant transformation. (February 2023)

• Record Type: Journal Article
• Authors: Li, Xinwei; Wang, Quankai; Wang, Miao; Wuhan, Baolier; Gu, Yiting; Kang, Tongying; Jin, Huiping; Xu, Jianning
• Is Part Of: Toxicology. Volume 485(2023)
• Publication Date: 2023-02
• Subjects: Glycidyl methacrylate -- Proteomic -- 16HBE cells -- Malignant transformation -- ECM-receptor; Toxicology -- Periodicals; Chemicals -- Physiological effect -- Periodicals; 615.9005
• DOI: 10.1016/j.tox.2023.153427
• Languages: English
• ISSNs: 0300-483X

Abstract

Abstract: Glycidyl methacrylate (GMA) has been widely used as tackifying/crosslinking copolymer monomer in the industrial section. Occupational and environmental exposure to GMA is inevitable. GMA is classified as a Group 2 A carcinogen. However, it still lacks a sufficient understanding of its carcinogenicity at the protein level. The major pathways and players during the malignant transformation process remain unknown. In this study, we first established and characterized a malignant transformation model using human bronchial epithelial (16HBE) cells exposed to 8 μg/mL GMA. Then the proteomics approach, western-blot analysis as well as quantitative PCR (qPCR) analysis were employed to investigate its underlying mechanisms of carcinogenicity. Our results showed that the 16HBE cells exposed to GMA and passaged to the 40th generation had undergone a malignant transformation. Proteomic analysis revealed that 123 proteins were significantly up-regulated while 160 proteins were down-regulated during the process of malignant transformation. Importantly, further pathway analysis identified the extracellular matrix-receptor (ECM-receptor) interaction pathway to be one of the major players mediating the process and most of the differentially expressed proteins (DEPs) were up-regulated, including two vital proteins, CD44 and MMP14, as well as members from integrin family. These results provide direct proteomic evidence that DEPs related to the ECM-receptor interaction pathway play an active role in reinforcing the carcinogenicity of GMA. The findings of this study might deepen our understanding of the underlying mechanisms of GMA carcinogenicity and thus facilitate the risk assessment of GMA. Graphical Abstract: ga1 Highlights: A malignant transformation cell model was established using 16HBE cell exposed to 8 μg/mL GMA. Proteomics and bioinformatics were employed to reveal the underlying mechanism. ECM-receptor interaction pathway is one of the main pathways and CD44, MMP14 are the major players. This study revealed the molecular mechanism underlying GMA carcinogenicity for the first time.