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  • CPAP enhances and maintains chronic inflammation in hepatocytes to promote hepatocarcinogenesis.

CPAP enhances and maintains chronic inflammation in hepatocytes to promote hepatocarcinogenesis.

Cell death & disease (2021-10-24)
Ruo-Yu Chen, Chia-Jui Yen, Yih-Jyh Lin, Ju-Ming Wang, Ting-Fen Tasi, Yu-Chuan Huang, Yao-Wen Liu, Hung-Wen Tsai, Ming-Hao Lee, Liang-Yi Hung
ABSTRACT

Chronic and persistent inflammation is a well-known carcinogenesis promoter. Hepatocellular carcinoma (HCC) is one of the most common inflammation-associated cancers; most HCCs arise in the setting of chronic inflammation and hepatic injury. Both NF-κB and STAT3 are important regulators of inflammation. Centrosomal P4.1-associated protein (CPAP), a centrosomal protein that participates primarily in centrosome functions, is overexpressed in HCC and can increase TNF-α-mediated NF-κB activation and IL-6-induced STAT3 activation. A transgenic (Tg) mouse model with hepatocyte-specific CPAP expression was established to investigate the physiological role of CPAP in hepatocarcinogenesis. Obvious inflammatory cell accumulation and fatty change were observed in the livers of CPAP Tg mice. The alanine aminotransferase (ALT) level and the expression levels of inflammatory genes, such as IL-6, IL-1β and TNF-α, were higher in CPAP Tg mice than in wild type (WT) mice. High-dose/short-term treatment with diethylnitrosamine (DEN) increased the ALT level, proinflammatory gene expression levels, and STAT3 and NF-κB activation in CPAP Tg mice; low-dose/long-term DEN treatment induced more severe liver tumor formation in CPAP Tg mice than in WT mice. CPAP can increase the expression of chemokine (C-C motif) ligand 16 (CCL-16), an important chemotactic cytokine, in human hepatocytes. CCL-16 expression is positively correlated with CPAP and TNF-α mRNA expression in the peritumoral part of HCC. In summary, these results suggest that CPAP may promote hepatocarcinogenesis through enhancing the inflammation pathway via increasing the expression of CCL-16.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Protease Inhibitor Cocktail, for use with mammalian cell and tissue extracts, DMSO solution
Sigma-Aldrich
N-Nitrosodiethylamine, liquid
Sigma-Aldrich
IL-6,
Human Recombinant Animal Free
Sigma-Aldrich
TNF- α Protein, Human Recombinant Animal Free, Tumor necrosis factor alpha (TNF-α), also known as cachectin & TNFSF1A, is the prototypic ligand of the TNF superfamily. Recombinant animal free human TNF-α is manufactured using all non-animal reagents.