1. High-fat diet induces C-reactive protein secretion, promoting lung adenocarcinoma via immune microenvironment modulation.
- Author
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Hsu WL, Hsieh YT, Chen WM, Chien MH, Luo WJ, Chang JH, Devlin K, and Su KY
- Subjects
- Mice, Animals, C-Reactive Protein, Diet, High-Fat, Mice, Transgenic, ErbB Receptors genetics, Tumor Microenvironment, Adenocarcinoma of Lung genetics, Lung Neoplasms genetics
- 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., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2023. Published by The Company of Biologists Ltd.)
- Published
- 2023
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