High-fat diet induces C-reactive protein secretion, promoting lung adenocarcinoma via immune microenvironment modulation
Journal
Disease models & mechanisms
Journal Volume
16
Journal Issue
11
Date Issued
2023-11-01
Author(s)
Hsu, Wei-Lun
Hsieh, Yun-Ting
Chen, Wei-Ming
Chien, Min-Hui
Luo, Wei-Jia
Chang, Jung-Hsuan
Devlin, Kevin
Abstract
To understand the effects of a high-fat diet (HFD) on lung cancer progression and biomarkers, we here used an inducible mutant epidermal growth factor receptor (EGFR)-driven lung cancer transgenic mouse model fed a regular diet (RD) or HFD. The HFD lung cancer (LC-HFD) group exhibited significant tumor formation and deterioration, such as higher EGFR activity and proliferation marker expression, compared with the RD lung cancer (LC-RD) group. Transcriptomic analysis of the lung tissues revealed that the significantly changed genes in the LC-HFD group were highly enriched in immune-related signaling pathways, suggesting that an HFD alters the immune microenvironment to promote tumor growth. Cytokine and adipokine arrays combined with a comprehensive analysis using meta-database software indicated upregulation of C-reactive protein (CRP) in the LC-HFD group, which presented with increased lung cancer proliferation and metastasis; this was confirmed experimentally. Our results imply that an HFD can turn the tumor growth environment into an immune-related pro-tumorigenic microenvironment and demonstrate that CRP has a role in promoting lung cancer development in this microenvironment.
Subjects
CRP; High-fat diet; Lung cancer; Mutant EGFR transgenic mice; Tumor microenvironment
SDGs
Type
journal article