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PrPC Glycoprotein Modulates Atmospherically Relevant Artificial Particulate Matter-Induced Development of Lung Cancer
Thi Thu Trang Kieu1, Hyun-Jaung Sim1,2, Govinda Bhattarai1,2
1Department of Bioactive Material Sciences, Research Center of Bioactive Materials, Jeonbuk National University, Jeonju 54896, Republic of Korea.
Environmental Science & Technology
|March 25, 2026
Summary
Cellular prion protein (PrPC) regulates susceptibility to lung cancer from fine particulate matter (PM2.5) exposure. Lower PrPC levels in older mice increase PM2.5-linked lung cancer risk.
Area of Science:
- Environmental Health
- Molecular Biology
- Oncology
Background:
- Fine particulate matter (PM2.5) is an environmental risk factor for lung cancer.
- The molecular mechanisms linking PM2.5 exposure to lung tumorigenesis are not fully understood.
- Aging is associated with increased susceptibility to PM2.5-induced lung pathologies.
Purpose of the Study:
- To investigate the role of cellular prion protein (PrPC) in PM2.5-induced lung cancer.
- To elucidate the molecular pathways involved in PM2.5-associated lung tumorigenesis.
- To compare the tumorigenic potential of different PM2.5 sources.
Main Methods:
- Exposure of wild-type and PrPC knockout mice to PM2.5 from synthetic and urban sources.
- Evaluation of lung pathology using imaging, histology, immunohistochemistry, and Western blotting.
- Analysis of the Sirt1-p53-HIF1α signaling axis.
Main Results:
- PrPC deficiency exacerbated age-associated lung pathologies, including emphysema, hypoxia, and angiogenesis.
- PM2.5 exposure in PrPC-deficient mice promoted tumorigenesis via dysregulation of the Sirt1-p53-HIF1α axis.
- Urban PM2.5 (NIST 1648a) induced more aggressive lung tumorigenesis compared to a synthetic mixture.
Conclusions:
- Cellular prion protein (PrPC) is a critical regulator of susceptibility to PM2.5-induced lung cancer.
- PM2.5 poses significant environmental and public health risks, especially for older adults.
- PrPC may serve as a mechanistic regulator and potential biomarker for pollution-associated lung cancer.
